Abstract

Here we present the results of a study concerning the effect of temperature on cell mechanical properties. Two different optofluidic microchips with external temperature control are used to investigate the temperature-induced changes of highly metastatic human melanoma cells (A375MC2) in the range of ~0 – 35 °C. By means of an integrated optical stretcher, we observe that cells’ optical deformability is strongly enhanced by increasing cell and buffer-fluid temperature. This finding is supported by the results obtained from a second device, which probes the cells’ ability to be squeezed through a constriction. Measured data demonstrate a marked dependence of cell mechanical properties on temperature, thus highlighting the importance of including a proper temperature-control system in the experimental apparatus.

© 2015 Optical Society of America

1. Introduction

It is well known that cell mechanics plays an important role in various cellular functions [1–4], and in many disease-related mutations, especially for carcinogenesis [5]. Besides, it was also demonstrated that cell's mechanical properties can be used as an intrinsic and reliable marker to distinguish between different cell types [6,7]. Cells’ cytoskeleton, the fundamental support and basic structure for cell mechanics, has a complex and dynamic framework mainly composed of actin filaments, microtubules and intermediate filaments, which continuously assemble and disassemble according to cell status. This dynamics can be modified by drugs, as well as by environment alterations, both internal to the cell or external [8]. In particular, the aforementioned processes of living cells are strongly temperature dependent because the relevant chemical reactions, the protein functionality and the constitutive materials are inherently temperature sensitive. Therefore, cellular mechanical properties can be affected by temperature changes. Different techniques for cell-mechanics study, ranging from micropipette aspiration to atomic force microscopy and optical stretching, have been extensively studied and summarized in literature [9]. Thermo-rheological experiments have been recently reported in literature [10], and optical stretchers have been exploited to analyze cell deformability as a function of environmental temperature, allowing to obtain detailed data about temperature-sensitive transient receptor potential vanilloid (TRPV2) and thermal unbinding of transient cross-links [11]. In this study, we investigate the temperature impact on cell mechanics by focusing on long-term temperature effect in a wide range of temperatures (~0 – 35 °C), especially in the low-temperature range. To evaluate the temperature-effect on cell mechanics, we used two integrated optofluidic microchips fabricated by 3D femtosecond laser micromachining [12], combined with an additional temperature control system: in the first chip (an optical stretcher, OS in the following) we exploit optical forces to induce cell deformation, whereas in the second one (a constriction-chip, CC in the following) we test cell mechanics in terms of their ability to passively squeeze through a small constriction.

2. Material and method

2.1 Optical stretcher

The OS, shown in Fig. 1 and already described in [13], was mounted on a phase contrast microscope equipped with a CCD camera. The input tube was connected to a vial containing the cell suspension, while the output one was immersed in water to avoid any possible pressure turbulence caused by droplet detachment or droplet size-variation during the experiments. The cell flow rate inside the microchip was regulated by an external micro-pump with high-precision pressure control (~1mbar). A CW Yb-doped fiber laser (PMAX = 10 W @ 1070 nm) was used as light source: the optical power was evenly split into two fibers and then coupled to the two waveguides of the chip through a single-mode optical fiber. The entire system was controlled using a custom LabVIEW program. The cell stretching experiment was based on the following procedure: low laser power (~25mW, Ptrap) was first emitted by each waveguide to capture a single cell [14]; the laser power was then raised to the “stretching power” (~1.2 W per side) for 5 s, and then reduced to Ptrap for 5 s more before releasing the cell. A video was recorded, at 15 fps, during the whole procedure.

 

Fig. 1 a) image of the optical stretcher chip; b) microchannel with two facing waveguides (not completely in focus). Yellow dashed line indicates the trapping/stretching region; c) and d) represent the same cell trapped and stretched respectively. Green contours are cell borders identified by the recognition algorithm.

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Thanks to the high imaging quality of the chip, and to the use of an edge detection algorithm [15], it was possible to recognize the contour of every measured cell, in each frame, with subpixel accuracy, as shown for example in Fig. 1(c)-1(d), thus allowing to extract the cellular deformation of each measured cell. By indicating with xorig (yorig) the initial cell dimension along the optical beams (and cell flowing) direction, the cell radius “RMS” was calculated using Eq. (1). Similarly, by indicating with xmax (ymin) the cell dimensions in the maximum deformation condition (see Fig. 1(d)), the maximum ellipticity variation (Var parameter) was evaluated using Eq. (2), where Corr is a correction factor taking into account the impact of different cell size on optical forces distribution [15,16].

RMS=(xorig2+yorig2)2
Var(%)=(xmaxyminyorigxorig1)100Corr

2.2 Constriction chip

The CC (see Fig. 2) has two inlets, connected to two vials, and two outlets with tubing dipped in water solution as for the OS. The core of the chip is similar to a cell sorter [17], but additionally the light output by a waveguide is used to apply a controlled force on selected cells, as indicated in the figure, sending them to the constriction. The operating principle of the CC is described in the following: one of the two inlets (inlet 2) is fed with a pure buffer solution and the other one (inlet 1) with the same buffer containing cells. By balancing the pressures of the two channels, a stable laminar flow is obtained in the central channel so that all of the cells coming from inlet 1 exit through outlet 1. When a cell must be tested, the laser source is turned on, sending the selected cell into the other stream (in the “lower part” of the central channel in Fig. 2), and making the selected cell to flow towards the constriction branch. When the sorted cell reaches the constriction, it stops flowing and partially clogs the channel. A slow pressure ramp (1 mbar/s) is then applied to inlet 2, so as to increase the force pushing the cell. The pressure required by each cell to passively squeeze through the constriction is defined as the “passing pressure” of that cell. It should be noted that, differently from conventional constrictions, the constriction length in our chip is very short (< 10μm), hence the experiment results are more related to the “cell entrance” into the constriction than to the cell passage through it. Due to friction and adhesion effects more deformable cells need a higher pressure to squeeze through the constriction, as discussed in [18].

 

Fig. 2 microscope image of constriction chip under bright field, locally enlarged constriction part has dimension of 8 × 12 μm2. Scare bar: 100μm

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2.3 Cell sample and temperature control

Highly metastatic human melanoma (A375MC2) [19] cell sample was obtained from the Cancer Research Center (Howard Hughes Medical Institute, MIT), cultured in Petri dishes and grown in Dulbecco’s Modified Eagle’s Medium supplemented with 10% Fetal Bovine Serum, penicillin (0.1 mg/ml), streptomicin (100 U/ml), 0.2 mM glutamine and 1X non-essential aminoacid (all by Euroclone). Cells were maintained into an incubator at 37°C in a humidified atmosphere at 5% CO2. For each measurement, 106 cells were plated in Petri dishes and detached about 24 h later by trypsinization. Cells were then suspended (2 × 105 cells/ml) in phosphate buffered saline (PBS) solution for each measurement.

Cells were tested at five temperatures: ~0°C, 5°C, 15°C, 25°C and 35°C, obtained by immersing the two chips, and a large part of the tubes, in a temperature controlled water bath. Thanks to a temperature sensor, positioned close to the measurement region, and by regularly flushing water at the desired temperature, we achieved a relatively stable setup temperature, with a maximum deviation from the desired value of ± 1°C, which is sufficient to avoid overlapping of the temperature intervals. To keep cells at the desired temperature, and to give to cells’ internal structures a relatively long time to re-organize, we kept the samples at the target temperature for 60 min before each measurement session.

3. Results and discussion

Given the variability of cell properties, > 60 cells were analyzed by OS and CC at every temperature. Measurements at ~0°C were performed using the OS only, to evaluate the impact of microtubule depolymerization, which was confirmed by fluorescent microscopy.

3.1 Cellular size and ellipticity

A first analysis of the cytoskeleton response to different temperatures was carried out by analyzing the change of cell size and ellipticity, defined as the ratio between horizontal and vertical dimension of the trapped cell. Cell size distribution at the different temperatures is reported in Fig. 3(a) while in Fig. 3(b) we show the measured cell ellipticity. Both data are presented as standard box plots, where the central squares indicate the measurement mean value, the central line for the median value, the box for interquartile range, the whiskers for 1%–99% and the external symbols for maximum/minimum values. It is evident that cell size is not significantly affected by temperature; however it is worth noticing that by increasing the temperature a rounder cell shape is generally observed (i.e. the ratio between x and y is closer to 1), offering a preliminary suggestion that the cell cytoskeleton could become softer when temperature is increased, thus more easily reaching the minimum-energy configuration.

 

Fig. 3 A375 MC2 cell size distribution a) and x/y ratio b) at different temperatures. Measurements were performed while trapping the cell by using the OS. Box width is not related to temperature variations.

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3.2 Optical deformation and passage through constrictions

In OS, cells under optical force show a creep compliance behavior [14,20]. The dependence of the maximum ellipticity variation (Var, see Eq. (2) on temperature is reported in Fig. 4(a), showing that higher values of Var are observed at higher temperatures, in agreement with results recently reported in literature [10,11]. In order to evaluate the significance of the differences, Mann-Whitney U-test was performed as the population was non-normal according to the Kolmogorov–Smirnov test. The obtained results on optical deformability showed a statistically significant difference (p < 10−3) between all the five temperatures.

 

Fig. 4 Optical deformation a) and passing pressure b) of A375 MC2 at different temperatures

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As known from literature [10,21,22], laser power can induce a sudden increase of the cell temperature, making it difficult to compare the deformation values obtained at different optical power levels. As in our case the same optical power is applied to all OS measurements, we expect an increase of about 30°C in the irradiated region for all the samples, provided that absorption coefficient changes due to the different temperatures are negligible. Consequently, the cells’ temperature-difference between the samples is maintained, thus not affecting the analysis of our results. Data reported in Fig. 4(a) also show that the increase of optical deformability is stronger at higher temperatures: a possible explanation for this effect is that more components of cytoskeleton and faster processes are involved at higher temperature; another possibility is that at higher temperature the cytosol viscosity decreases, allowing for smoother and faster cells’ shape changes [11], and coherently with the ellipticity data reported in Fig. 3(b). It is worth discussing the results obtained by measuring cells kept at ~0 °C, as microtubules, considered as rigid cytoskeletal component [23], are known to depolymerize at low temperatures [24,25]. Even if a higher optical deformability of cells could be intuitively expected, we observed a slight decrease of Var, with respect to the value obtained at 5°C, thus confirming that microtubules do not have a major impact on cell compliance measurements performed by OS, as suggested in [26].

Cell ability to pass through a microchannel with a cross-section significantly smaller than the cell itself attracted much attention [1,27], as this feature is particularly evident in metastatic cells, thus suggesting its use for cells’ diagnostics, or for new drugs testing. Figure 4(b) reports the experimental results obtained with the CC chip by applying the procedure described in section 2.2. The results show that the passing pressure of A375MC2 gradually increases with temperature: this means that cell passive-squeezing through the constriction is hindered by the high temperature, as a higher pressure (i.e. a stronger force) is required to push the cell through the CC. These results are in good agreement with those already reported in [18] about mechanical properties of cells undergoing different drugs treatments: softer cells (in that case modified by drug-treatments) required higher pressures to be squeezed through the constriction. This is due to the fact that more deformable cells create a larger contact area between the cell and the constriction entrance, hence increasing the overall friction and requiring a higher passing pressure. Regarding the results reported in Fig. 4(b) statistically significant differences were obtained comparing the different samples, always by exploiting the Mann-Whitney U-test, with the only exclusion of the 15°C-25°C comparison.

It is interesting to underline that, not being affected by any laser-induced “temperature-shift”, the CC measurements at high temperature confirm the deformability trends observed by OS. In addition the low-temperature CC measurements allow investigating cells’ properties in a significantly different range of cell-temperatures. As a final remark regarding the cell viability, it is worth noting that in the case of stretching experiments performed on cells initially at 35°C, the impact of temperature on their viability has to be carefully considered [21], since during the measurement the cell is expected to exceed the damage-threshold temperature. Conversely, if low-temperature investigations are conducted, the effect of 5-s heating on viability is generally negligible, as discussed in [7].

4. Conclusion

By using two temperature controlled optofluidic microchips we analyzed the changes of metastatic cells’ mechanical properties induced by temperature variations. It is observed that cell optical deformability is strongly increased by raising cell temperature. Additionally, cellular ability to passively-squeeze through a constriction was investigated, and the obtained results prove that as temperature is increased a higher pressure is required for cell passage. As this behavior was observed for softer cells, these results strongly support those obtained by using the optical stretcher. Overall, results demonstrate that cell mechanical properties are strongly dependent on temperature, and that as the temperature is increased the cell appears much softer. Although cellular mechanics is a very complex process, this study shows that even moderate temperature variations can induce a clear modification of cells’ properties (e.g. + 1% optical deformation for a 2°C temperature increase), thus highlighting the importance of a proper temperature control, both in experimental setups for cell mechanics evaluation, and to carry out comparisons between different samples.

Acknowledgements

The authors acknowledge financial support by Fondazione Cariplo through the project “Optofluidic chips for the study of cancer cell mechanical properties and invasive capacities”.

References and links

1. S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3(4), 413–438 (2007). [CrossRef]   [PubMed]  

2. F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994). [CrossRef]   [PubMed]  

3. W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012). [CrossRef]   [PubMed]  

4. C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012). [CrossRef]   [PubMed]  

5. A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010). [CrossRef]  

6. C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015). [CrossRef]   [PubMed]  

7. T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015). [CrossRef]   [PubMed]  

8. T. D. Pollard and G. G. Borisy, “Cellular motility driven by assembly and disassembly of actin filaments,” Cell 112(4), 453–465 (2003). [CrossRef]   [PubMed]  

9. M. R. K. Mofrad and R. D. Kamm, eds., “Cytoskeletal Mechanics: Models and Measurements in Cell Mechanics,” Cambridge University Press, (2011).

10. T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013). [CrossRef]  

11. C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014). [CrossRef]   [PubMed]  

12. R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007). [CrossRef]  

13. N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012). [CrossRef]   [PubMed]  

14. B. Lincoln, F. Wottawah, S. Schinkinger, S. Ebert, and J. Guck, “High Throughput Rheological Measurements with an Optical Stretcher,” in Methods in Cell Biology, W. Yu-Li and E. D. Dennis, eds., Academic Press 83, 397–423 (2007)

15. J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001). [CrossRef]   [PubMed]  

16. J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005). [CrossRef]   [PubMed]  

17. F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012). [CrossRef]   [PubMed]  

18. R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015). [CrossRef]   [PubMed]  

19. L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006). [CrossRef]   [PubMed]  

20. F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005). [CrossRef]   [PubMed]  

21. F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011). [CrossRef]   [PubMed]  

22. S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007). [CrossRef]   [PubMed]  

23. H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, and J. Darnell, “Molecular Cell Biology,” New York: W. H. Freeman (2000).

24. L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986). [CrossRef]   [PubMed]  

25. E. M. Faller and D. L. Brown, “Modulation of microtubule dynamics by the microtubule-associated protein 1a,” J. Neurosci. Res. 87(5), 1080–1089 (2009). [CrossRef]   [PubMed]  

26. F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009). [CrossRef]   [PubMed]  

27. B. Yap and R. D. Kamm, “Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties,” J. Appl. Physiol. 98(5), 1930–1939 (2005). [CrossRef]   [PubMed]  

References

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  1. S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3(4), 413–438 (2007).
    [Crossref] [PubMed]
  2. F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
    [Crossref] [PubMed]
  3. W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
    [Crossref] [PubMed]
  4. C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
    [Crossref] [PubMed]
  5. A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
    [Crossref]
  6. C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
    [Crossref] [PubMed]
  7. T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
    [Crossref] [PubMed]
  8. T. D. Pollard and G. G. Borisy, “Cellular motility driven by assembly and disassembly of actin filaments,” Cell 112(4), 453–465 (2003).
    [Crossref] [PubMed]
  9. M. R. K. Mofrad and R. D. Kamm, eds., “Cytoskeletal Mechanics: Models and Measurements in Cell Mechanics,” Cambridge University Press, (2011).
  10. T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
    [Crossref]
  11. C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
    [Crossref] [PubMed]
  12. R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
    [Crossref]
  13. N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
    [Crossref] [PubMed]
  14. B. Lincoln, F. Wottawah, S. Schinkinger, S. Ebert, and J. Guck, “High Throughput Rheological Measurements with an Optical Stretcher,” in Methods in Cell Biology, W. Yu-Li and E. D. Dennis, eds., Academic Press 83, 397–423 (2007)
  15. J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
    [Crossref] [PubMed]
  16. J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
    [Crossref] [PubMed]
  17. F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
    [Crossref] [PubMed]
  18. R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
    [Crossref] [PubMed]
  19. L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
    [Crossref] [PubMed]
  20. F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
    [Crossref] [PubMed]
  21. F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
    [Crossref] [PubMed]
  22. S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007).
    [Crossref] [PubMed]
  23. H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, and J. Darnell, “Molecular Cell Biology,” New York: W. H. Freeman (2000).
  24. L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986).
    [Crossref] [PubMed]
  25. E. M. Faller and D. L. Brown, “Modulation of microtubule dynamics by the microtubule-associated protein 1a,” J. Neurosci. Res. 87(5), 1080–1089 (2009).
    [Crossref] [PubMed]
  26. F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
    [Crossref] [PubMed]
  27. B. Yap and R. D. Kamm, “Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties,” J. Appl. Physiol. 98(5), 1930–1939 (2005).
    [Crossref] [PubMed]

2015 (3)

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

2014 (1)

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

2013 (1)

T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
[Crossref]

2012 (4)

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

2011 (1)

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

2010 (1)

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

2009 (2)

E. M. Faller and D. L. Brown, “Modulation of microtubule dynamics by the microtubule-associated protein 1a,” J. Neurosci. Res. 87(5), 1080–1089 (2009).
[Crossref] [PubMed]

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

2007 (3)

S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3(4), 413–438 (2007).
[Crossref] [PubMed]

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007).
[Crossref] [PubMed]

2006 (1)

L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
[Crossref] [PubMed]

2005 (3)

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

B. Yap and R. D. Kamm, “Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties,” J. Appl. Physiol. 98(5), 1930–1939 (2005).
[Crossref] [PubMed]

2003 (1)

T. D. Pollard and G. G. Borisy, “Cellular motility driven by assembly and disassembly of actin filaments,” Cell 112(4), 453–465 (2003).
[Crossref] [PubMed]

2001 (1)

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

1994 (1)

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

1986 (1)

L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986).
[Crossref] [PubMed]

Ananthakrishnan, R.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

Begum, S.

L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
[Crossref] [PubMed]

Beil, M.

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

Bellini, N.

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

Bianchi, E.

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

Bilby, C.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Blatt, T.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Borisy, G. G.

T. D. Pollard and G. G. Borisy, “Cellular motility driven by assembly and disassembly of actin filaments,” Cell 112(4), 453–465 (2003).
[Crossref] [PubMed]

Bosch, F. H.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Boyde, L.

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

Bragheri, F.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

Brown, D. L.

E. M. Faller and D. L. Brown, “Modulation of microtubule dynamics by the microtubule-associated protein 1a,” J. Neurosci. Res. 87(5), 1080–1089 (2009).
[Crossref] [PubMed]

Bruel, A.

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

Cassimeris, L. U.

L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986).
[Crossref] [PubMed]

Cerullo, G.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

Chan, C. J.

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

Chang, J.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Chiodi, I.

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

Choi, D. S.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Cristiani, I.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

Cunningham, C. C.

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

Di Tano, M.

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

Ebert, S.

S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Erickson, H. M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Faigle, C.

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

Faller, E. M.

E. M. Faller and D. L. Brown, “Modulation of microtubule dynamics by the microtubule-associated protein 1a,” J. Neurosci. Res. 87(5), 1080–1089 (2009).
[Crossref] [PubMed]

Fritsch, A.

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Fritsch, A. W.

T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
[Crossref]

Guck, J.

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

Gyger, M.

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

Halie, M. R.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Hearn, J. D.

L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
[Crossref] [PubMed]

Höckel, M.

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Homewood, P.

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

Huls, T.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Hynes, R. O.

L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
[Crossref] [PubMed]

Iwamoto, T.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Jaspers, S.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Kai, K.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Kamm, R. D.

B. Yap and R. D. Kamm, “Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties,” J. Appl. Physiol. 98(5), 1930–1939 (2005).
[Crossref] [PubMed]

Käs, J.

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

Käs, J. A.

T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
[Crossref]

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Kiessling, T.

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Kießling, T. R.

T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
[Crossref]

Kueper, T.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Landis, M. D.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Lautenschläger, F.

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

Lenz, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Lincoln, B.

S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Mahmood, H.

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

Malsen, A.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Martín-Badosa, E.

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

Martinez Vazquez, R.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

Maselli, V.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

Minzioni, P.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

Mitchell, D.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Mondello, C.

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

Moon, T. J.

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

Muhr, G.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Müller, K.

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

Nava, G.

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

Nguyen, Y. H.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Nnetu, K. D.

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Osellame, R.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

Paiè, P.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

Paschke, S.

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

Pollard, T. D.

T. D. Pollard and G. G. Borisy, “Cellular motility driven by assembly and disassembly of actin filaments,” Cell 112(4), 453–465 (2003).
[Crossref] [PubMed]

Qin, L.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Ramponi, R.

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

Roerdinkholder-Stoelwinder, B.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Romeyke, M.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Rönicke, S.

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

Rose, D.

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

Salbreux, G.

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

Salmon, E. D.

L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986).
[Crossref] [PubMed]

Sauer, F.

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

Schinkinger, S.

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Schipper, L.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Schulze, C.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Stange, R.

T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
[Crossref]

Suresh, S.

S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3(4), 413–438 (2007).
[Crossref] [PubMed]

Travis, K.

S. Ebert, K. Travis, B. Lincoln, and J. Guck, “Fluorescence ratio thermometry in a microfluidic dual-beam laser trap,” Opt. Express 15(23), 15493–15499 (2007).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

Ueno, N. T.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Ulvick, S.

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Vazquez, R. M.

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

Veglione, M.

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

Wadsworth, P.

L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986).
[Crossref] [PubMed]

Wenck, H.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Werre, J. M.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Wetzel, F.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Whyte, G.

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

N. Bellini, F. Bragheri, I. Cristiani, J. Guck, R. Osellame, and G. Whyte, “Validation and perspectives of a femtosecond laser fabricated monolithic optical stretcher,” Biomed. Opt. Express 3(10), 2658–2668 (2012).
[Crossref] [PubMed]

Wichers, G.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Willekens, F. L. A.

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Wittern, K.-P.

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Wong, H.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Wottawah, F.

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Xu, L.

L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
[Crossref] [PubMed]

Yang, T.

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

Yap, B.

B. Yap and R. D. Kamm, “Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties,” J. Appl. Physiol. 98(5), 1930–1939 (2005).
[Crossref] [PubMed]

Zhang, W.

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Zink, M.

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

Acta Biomater. (2)

S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Biomater. 3(4), 413–438 (2007).
[Crossref] [PubMed]

F. Wottawah, S. Schinkinger, B. Lincoln, S. Ebert, K. Müller, F. Sauer, K. Travis, and J. Guck, “Characterizing single suspended cells by optorheology,” Acta Biomater. 1(3), 263–271 (2005).
[Crossref] [PubMed]

Appl. Phys. Lett. (1)

R. Osellame, V. Maselli, R. M. Vazquez, R. Ramponi, and G. Cerullo, “Integration of optical waveguides and microfluidic channels both fabricated by femtosecond laser irradiation,” Appl. Phys. Lett. 90(23), 231118 (2007).
[Crossref]

Biomed. Opt. Express (1)

Biophys. J. (2)

J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,” Biophys. J. 81(2), 767–784 (2001).
[Crossref] [PubMed]

J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence,” Biophys. J. 88(5), 3689–3698 (2005).
[Crossref] [PubMed]

Cell (1)

T. D. Pollard and G. G. Borisy, “Cellular motility driven by assembly and disassembly of actin filaments,” Cell 112(4), 453–465 (2003).
[Crossref] [PubMed]

Clin. Plast. Surg. (1)

C. Schulze, F. Wetzel, T. Kueper, A. Malsen, G. Muhr, S. Jaspers, T. Blatt, K.-P. Wittern, H. Wenck, and J. A. Käs, “Stiffening of Human Skin Fibroblasts with Age,” Clin. Plast. Surg. 39(1), 9–20 (2012).
[Crossref] [PubMed]

Eur. Biophys. J. (1)

F. Wetzel, S. Rönicke, K. Müller, M. Gyger, D. Rose, M. Zink, and J. Käs, “Single cell viability and impact of heating by laser absorption,” Eur. Biophys. J. 40(9), 1109–1114 (2011).
[Crossref] [PubMed]

Eur. J. Haematol. (1)

F. H. Bosch, J. M. Werre, L. Schipper, B. Roerdinkholder-Stoelwinder, T. Huls, F. L. A. Willekens, G. Wichers, and M. R. Halie, “Determinants of red blood cell deformability in relation to cell age,” Eur. J. Haematol. 52(1), 35–41 (1994).
[Crossref] [PubMed]

Integr Biol (Camb) (1)

R. Martinez Vazquez, G. Nava, M. Veglione, T. Yang, F. Bragheri, P. Minzioni, E. Bianchi, M. Di Tano, I. Chiodi, R. Osellame, C. Mondello, and I. Cristiani, “An optofluidic constriction chip for monitoring metastatic potential and drug response of cancer cells,” Integr Biol (Camb) 7(4), 477–484 (2015).
[Crossref] [PubMed]

Interface Focus (1)

C. J. Chan, G. Whyte, L. Boyde, G. Salbreux, and J. Guck, “Impact of heating on passive and active biomechanics of suspended cells,” Interface Focus 4(2), 20130069 (2014).
[Crossref] [PubMed]

J. Appl. Physiol. (1)

B. Yap and R. D. Kamm, “Mechanical deformation of neutrophils into narrow channels induces pseudopod projection and changes in biomechanical properties,” J. Appl. Physiol. 98(5), 1930–1939 (2005).
[Crossref] [PubMed]

J. Cell Biol. (1)

L. U. Cassimeris, P. Wadsworth, and E. D. Salmon, “Dynamics of microtubule depolymerization in monocytes,” J. Cell Biol. 102(6), 2023–2032 (1986).
[Crossref] [PubMed]

J. Neurosci. Res. (1)

E. M. Faller and D. L. Brown, “Modulation of microtubule dynamics by the microtubule-associated protein 1a,” J. Neurosci. Res. 87(5), 1080–1089 (2009).
[Crossref] [PubMed]

Lab Chip (3)

F. Bragheri, P. Minzioni, R. Martinez Vazquez, N. Bellini, P. Paiè, C. Mondello, R. Ramponi, I. Cristiani, and R. Osellame, “Optofluidic integrated cell sorter fabricated by femtosecond lasers,” Lab Chip 12(19), 3779–3784 (2012).
[Crossref] [PubMed]

C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab Chip 15(5), 1267–1275 (2015).
[Crossref] [PubMed]

T. Yang, P. Paiè, G. Nava, F. Bragheri, R. Martinez Vazquez, P. Minzioni, M. Veglione, M. Di Tano, C. Mondello, R. Osellame, and I. Cristiani, “An integrated optofluidic device for single-cell sorting driven by mechanical properties,” Lab Chip 15(5), 1262–1266 (2015).
[Crossref] [PubMed]

Nat. Phys. (1)

A. Fritsch, M. Höckel, T. Kiessling, K. D. Nnetu, F. Wetzel, M. Zink, and J. A. Käs, “Are biomechanical changes necessary for tumour progression?” Nat. Phys. 6(10), 730–732 (2010).
[Crossref]

New J. Phys. (1)

T. R. Kießling, R. Stange, J. A. Käs, and A. W. Fritsch, “Thermorheology of living cells-impact of temperature variations on cell mechanics,” New J. Phys. 15(4), 045026 (2013).
[Crossref]

Opt. Express (1)

Proc. Natl. Acad. Sci. U.S.A. (3)

F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proc. Natl. Acad. Sci. U.S.A. 106(37), 15696–15701 (2009).
[Crossref] [PubMed]

L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes, “GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis,” Proc. Natl. Acad. Sci. U.S.A. 103(24), 9023–9028 (2006).
[Crossref] [PubMed]

W. Zhang, K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” Proc. Natl. Acad. Sci. U.S.A. 109(46), 18707–18712 (2012).
[Crossref] [PubMed]

Other (3)

M. R. K. Mofrad and R. D. Kamm, eds., “Cytoskeletal Mechanics: Models and Measurements in Cell Mechanics,” Cambridge University Press, (2011).

B. Lincoln, F. Wottawah, S. Schinkinger, S. Ebert, and J. Guck, “High Throughput Rheological Measurements with an Optical Stretcher,” in Methods in Cell Biology, W. Yu-Li and E. D. Dennis, eds., Academic Press 83, 397–423 (2007)

H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore, and J. Darnell, “Molecular Cell Biology,” New York: W. H. Freeman (2000).

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Figures (4)

Fig. 1
Fig. 1 a) image of the optical stretcher chip; b) microchannel with two facing waveguides (not completely in focus). Yellow dashed line indicates the trapping/stretching region; c) and d) represent the same cell trapped and stretched respectively. Green contours are cell borders identified by the recognition algorithm.
Fig. 2
Fig. 2 microscope image of constriction chip under bright field, locally enlarged constriction part has dimension of 8 × 12 μm2. Scare bar: 100μm
Fig. 3
Fig. 3 A375 MC2 cell size distribution a) and x/y ratio b) at different temperatures. Measurements were performed while trapping the cell by using the OS. Box width is not related to temperature variations.
Fig. 4
Fig. 4 Optical deformation a) and passing pressure b) of A375 MC2 at different temperatures

Equations (2)

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RMS= ( x orig 2 + y orig 2 ) 2
Var(%)=( x max y min y orig x orig 1 )100Corr

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