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In pursuit of the mechanics that shape cell surfaces

Abstract

Robust and responsive, the surface of a cell is as important as its interior when it comes to mechanically regulating form and function. New techniques are shedding light on this role, and a common language to describe its properties is now needed.

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Fig. 1: Schematics of methods to characterize the cell surface.

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References

  1. Mayor, R. & Etienne-Manneville, S. The front and rear of collective cell migration. Nat. Rev. Mol. Cell Biol. 17, 97–109 (2016).

    Google Scholar 

  2. Ridley, A. J. Rho GTPase signalling in cell migration. Curr. Opin. Cell Biol. 36, 103–112 (2015).

    Google Scholar 

  3. Raucher, D. & Sheetz, M. P. Cell spreading and lamellipodial extension rate is regulated by membrane tension. J. Cell Biol. 148, 127–136 (2000).

    Google Scholar 

  4. Gauthier, N. C., Fardin, M. A., Roca-Cusachs, P. & Sheetz, M. P. Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading. Proc. Natl Acad. Sci. USA 108, 11467–11472 (2011).

    Google Scholar 

  5. Keren, K. et al. Mechanism of shape determination in motile cells. Nature 453, 475–480 (2008).

    ADS  Google Scholar 

  6. Mitchison, T. & Cramer, L. Actin-based cell motility and cell locomotion. Cell 84, 371–379 (1996).

    Google Scholar 

  7. Houk, A. R. et al. Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148, 175–188 (2012).

    Google Scholar 

  8. Kozlov, M. M. & Mogilner, A. Model of polarization and bistability of cell fragments. Biophys. J. 93, 3811–3819 (2007).

    ADS  Google Scholar 

  9. Diz-Muñoz, A. et al. Membrane tension acts through PLD2 and mTORC2 to limit actin network assembly during neutrophil migration. PLoS Biol. 14, e1002474 (2016).

    Google Scholar 

  10. Tsujita, K., Takenawa, T. & Itoh, T. Feedback regulation between plasma membrane tension and membrane-bending proteins organizes cell polarity during leading edge formation. Nat. Cell Biol. 17, 749–758 (2015).

    Google Scholar 

  11. Lieber, A. D., Schweitzer, Y., Kozlov, M. M. & Keren, K. Front-to-rear membrane tension gradient in rapidly moving cells. Biophys. J. 108, 1599–1603 (2015).

    ADS  Google Scholar 

  12. Iskratsch, T., Wolfenson, H. & Sheetz, M. P. Appreciating force and shape — the rise of mechanotransduction in cell biology. Nat. Rev. Mol. Cell Biol. 15, 825–833 (2014).

    Google Scholar 

  13. Atilla-Gokcumen, G. E. et al. Dividing cells regulate their lipid composition and localization. Cell 156, 428–439 (2014).

    Google Scholar 

  14. Dai, J. & Sheetz, M. P. Membrane tether formation from blebbing cells. Biophys. J. 77, 3363–3370 (1999).

    Google Scholar 

  15. Hayashi, K., Yonemura, S., Matsui, T. & Tsukita, S. Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues. J. Cell Sci. 112, 1149–1158 (1999).

    Google Scholar 

  16. Link, V. et al. Identification of regulators of germ layer morphogenesis using proteomics in zebrafish. J. Cell Sci. 119, 2073–2083 (2006).

    Google Scholar 

  17. Bennett, V. & Baines, A. J. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol. Rev. 81, 1353–1392 (2001).

    Google Scholar 

  18. Krieg, M., Dunn, A. R. & Goodman, M. B. Mechanical control of the sense of touch by β-spectrin. Nat. Cell Biol. 16, 224–233 (2014).

    Google Scholar 

  19. Gaetani, M., Mootien, S., Harper, S., Gallagher, P. G. & Speicher, D. W. Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site. Blood 111, 5712–5720 (2008).

    Google Scholar 

  20. Ikeda, Y. et al. Spectrin mutations cause spinocerebellar ataxia type 5. Nat. Genet. 38, 184–190 (2006).

    Google Scholar 

  21. Simunovic, M. et al. Friction mediates scission of tubular membranes scaffolded by BAR proteins. Cell 170, 172–184 (2017).

    Google Scholar 

  22. Lewis, A. H. & Grandl, J. Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. eLife 4, (2015).

  23. Evans, E. A. Bending elastic modulus of red blood cell membrane derived from buckling instability in micropipet aspiration tests. Biophys. J. 43, 27–30 (1983).

    ADS  Google Scholar 

  24. Hochmuth, F. M., Shao, J. Y., Dai, J. & Sheetz, M. P. Deformation and flow of membrane into tethers extracted from neuronal growth cones. Biophys. J. 70, 358–369 (1996).

    Google Scholar 

  25. Charras, G. & Paluch, E. Blebs lead the way: how to migrate without lamellipodia. Nat. Rev. Mol. Cell Biol. 9, 730–736 (2008).

    Google Scholar 

  26. Sens, P. & Plastino, J. Membrane tension and cytoskeleton organization in cell motility. J. Phys. Condens. Matter 27, 273103 (2015).

    ADS  Google Scholar 

  27. Sheetz, M. Cell control by membrane-cytoskeleton adhesion. Nat. Rev. Mol. Cell Biol. 2, 392–396 (2001).

    Google Scholar 

  28. Sun, M. et al. Multiple membrane tethers probed by atomic force microscopy. Biophys. J. 89, 4320–4329 (2005).

    ADS  Google Scholar 

  29. Sun, M. et al. The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J. Cell Sci. 120, 2223–2231 (2007).

    Google Scholar 

  30. Brochard-Wyart, F., Borghi, N., Cuvelier, D. & Nassoy, P. Hydrodynamic narrowing of tubes extruded from cells. Proc. Natl Acad. Sci. USA 103, 7660–7663 (2006).

    ADS  Google Scholar 

  31. Waugh, R. & Evans, E. A. Thermoelasticity of red blood cell membrane. Biophys. J. 26, 115–131 (1979).

    ADS  Google Scholar 

  32. Dimova, R. Advances in Colloid and Interface Science. Adv. Colloid Interface Sci. 208, 225–234 (2014).

    Google Scholar 

  33. Salbreux, G., Charras, G. & Paluch, E. Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol. 22, 536–545 (2012).

    Google Scholar 

  34. Chugh, P. et al. Actin cortex architecture regulates cell surface tension. Nat. Cell Biol. 19, 689–697 (2017).

    Google Scholar 

  35. Bovellan, M. et al. Cellular control of cortical actin nucleation. Curr. Biol. 24, 1628–1635 (2014).

    Google Scholar 

  36. Fritzsche, M., Erlenka mper, C., Moeendarbary, E., Charras, G. & Kruse, K. Actin kinetics shapes cortical network structure and mechanics. Sci. Adv. 2, e1501337 (2016).

    ADS  Google Scholar 

  37. Suarez, C. & Kovar, D. R. Internetwork competition for monomers governs actin cytoskeleton organization. Nat. Rev. Mol. Cell Biol. 17, 799–810 (2016).

    Google Scholar 

  38. Evans, E. & Yeung, A. Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration. Biophys. J. 56, 151–160 (1989).

    ADS  Google Scholar 

  39. Dai, J., Ting-Beall, H. P., Hochmuth, R. M., Sheetz, M. P. & Titus, M. A. Myosin I contributes to the generation of resting cortical tension. Biophys. J. 77, 1168–1176 (1999).

    Google Scholar 

  40. Schwarz, E. C., Neuhaus, E. M., Kistler, C., Henkel, A. W. & Soldati, T. Dictyostelium myosin IK is involved in the maintenance of cortical tension and affects motility and phagocytosis. J. Cell Sci. 113, 621–633 (2000).

    Google Scholar 

  41. Ledesma, M. D. & Dotti, C. G. Membrane and cytoskeleton dynamics during axonal elongationand stabilization. Int. Rev. Cytol. 227, 183–219 (2003).

    Google Scholar 

  42. Diz-Muñoz, A. et al. Control of directed cell migration in vivo by membrane-to-cortex attachment. PLoS Biol. 8, e1000544 (2010).

    Google Scholar 

  43. Bieling, P. et al. Force feedback controls motor activity and mechanical properties of self-assembling branched actin networks. Cell 164, 115–127 (2016).

    Google Scholar 

  44. Betz, T., Lenz, M., Joanny, J.-F. & Sykes, C. ATP-dependent mechanics of red blood cells. Proc. Natl Acad. Sci. USA 106, 15320–15325 (2009).

    ADS  Google Scholar 

  45. Pontes, B. et al. Membrane tension controls adhesion positioning at the leading edge of cells. J. Cell Biol. 216, 2959 (2017).

    Google Scholar 

  46. Schmidtke, D. W. & Diamond, S. L. Direct observation of membrane tethers formed during neutrophil attachment to platelets or P-selectin under physiological flow. J. Cell Biol. 149, 719–730 (2000).

    Google Scholar 

  47. Fischer-Friedrich, E., Hyman, A. A., Jülicher, F., Muller, D. J. & Helenius, J. Quantification of surface tension and internal pressure generated by single mitotic cells. Sci. Rep. 4, 137 (2014).

    Google Scholar 

  48. Yoneda, M. & Dan, K. Tension at the surface of the dividing sea-urchin egg. J. Exp. Biol. 57, 575–587 (1972).

    Google Scholar 

  49. Mayer, M., Depken, M., Bois, J. S., Jülicher, F. & Grill, S. W. Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows. Nature 467, 617–621 (2010).

    ADS  Google Scholar 

  50. Rosenbluth, M. J., Lam, W. A. & Fletcher, D. A. Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. Biophys. J. 90, 2994–3003 (2006).

    ADS  Google Scholar 

  51. Elsayad, K. et al. Mapping the subcellular mechanical properties of live cells in tissues with fluorescence emission-Brillouin imaging. Sci. Signal. 9, rs5 (2016).

    Google Scholar 

  52. Antonacci, G. & Braakman, S. Biomechanics of subcellularstructures by non-invasive Brillouin microscopy. Sci. Rep. 6, 37217 (2016).

    ADS  Google Scholar 

  53. Coughlin, M. F. et al. Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin. Exp. Metastasis 30, 237–250 (2012).

    Google Scholar 

  54. Hanakam, F., Albrecht, R., Eckerskorn, C., Matzner, M. & Gerisch, G. Myristoylated and non-myristoylated forms of the pH sensor protein hisactophilin II: intracellular shuttling to plasma membrane and nucleus monitored in real time by a fusion with green fluorescent protein. EMBO J. 15, 2935–2943 (1996).

    Google Scholar 

  55. Clark, A. G., Dierkes, K. & Paluch, E. K. Monitoring actin cortex thickness in live cells. Biophys. J. 105, 570–580 (2013).

    ADS  Google Scholar 

  56. Zhelev, D. V., Needham, D. & Hochmuth, R. M. Role of the membrane cortex in neutrophil deformation in small pipets. Biophys. J. 67, 696–705 (1994).

    ADS  Google Scholar 

  57. Fricke, K., Wirthensohn, K., Laxhuber, R. & Sackmann, E. Flicker spectroscopy of erythrocytes. A sensitive method to study subtle changes of membrane bending stiffness. Eur. Biophys. J. 14, 67–81 (1986).

    Google Scholar 

  58. López-Duarte, I., Vu, T. T., Izquierdo, M. A., Bull, J. A. & Kuimova, M. K. A molecular rotor for measuring viscosity in plasma membranes of live cells. Chem. Commun. 50, 5282–5284 (2014).

    Google Scholar 

  59. Campàs, O. A toolbox to explore the mechanics of living embryonic tissues. Semin. Cell Dev. Biol. 55, 119–130 (2016).

    Google Scholar 

  60. Sugimura, K., Lenne, P. F. & Graner, F. Measuring forces and stresses in situ in living tissues. Development 143, 186–196 (2016).

    Google Scholar 

  61. Polacheck, W. J. & Chen, C. S. Measuring cell-generated forces: a guide to the available tools. Nat. Methods 13, 415–423 (2016).

    Google Scholar 

  62. Roca-Cusachs, P., Conte, V. & Trepat, X. Quantifying forces in cell biology. Nat. Cell Biol. 19, 742–751 (2017).

    Google Scholar 

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Acknowledgements

We thank M. Bergert for comments on the manuscript and the schematics in Fig. 1. We acknowledge the financial support of the European Molecular Biology Laboratory (A.D.-M.), the NIH through GM114671 (D.A.F.), GM114344 (D.A.F) and GM118167 (O.D.W.), and the Chan Zuckerberg Biohub (D.A.F.).

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Correspondence to Alba Diz-Muñoz or Daniel A. Fletcher.

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Diz-Muñoz, A., Weiner, O.D. & Fletcher, D.A. In pursuit of the mechanics that shape cell surfaces. Nature Phys 14, 648–652 (2018). https://doi.org/10.1038/s41567-018-0187-8

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