Review Article | Published:

Mechanoreciprocity in cell migration

Nature Cell Biologyvolume 20pages820 (2018) | Download Citation

Abstract

Cell migration is an adaptive process that depends on and responds to physical and molecular triggers. Moving cells sense and respond to tissue mechanics and induce transient or permanent tissue modifications, including extracellular matrix stiffening, compression and deformation, protein unfolding, proteolytic remodelling and jamming transitions. Here we discuss how the bi-directional relationship of cell–tissue interactions (mechanoreciprocity) allows cells to change position and contributes to single-cell and collective movement, structural and molecular tissue organization, and cell fate decisions.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    Gardel, M. L., Schneider, I. C., Aratyn-Schaus, Y. & Waterman, C. M. Mechanical integration of actin and adhesion dynamics in cell migration. Annu. Rev. Cell Dev. Biol. 26, 315–333 (2010).

  2. 2.

    Charras, G. & Sahai, E. Physical influences of the extracellular environment on cell migration. Nat. Rev. Mol. Cell Biol. 15, 813–824 (2014).

  3. 3.

    te Boekhorst, V., Preziosi, L. & Friedl, P. Plasticity of cell migration in vivo and in silico. Annu. Rev. Cell Dev. Biol. 32, 491–526 (2016).

  4. 4.

    Bornstein, P., McPherson, J. & Sage, H. in Pathobiology of the Endothelial Cell (eds Nossel, H. & Vogel, H.) 215–228 (Academic Press, New York, 1982).

  5. 5.

    Bissell, M. J., Hall, H. G. & Parry, G. How does the extracellular matrix direct gene expression? J. Theor. Biol. 99, 31–68 (1982).

  6. 6.

    Friedl, P. & Alexander, S. Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147, 992–1009 (2011).

  7. 7.

    Paul, C. D., Hung, W.-C., Wirtz, D. & Konstantopoulos, K. Engineered models of confined cell migration. Annu. Rev. Biomed. Eng. 18, 159–180 (2016).

  8. 8.

    de Almeida, P. G., Pinheiro, G. G., Nunes, A. M., Gonçalves, A. B. & Thorsteinsdóttir, S. Fibronectin assembly during early embryo development: a versatile communication system between cells and tissues. Dev. Dyn. 245, 520–535 (2016).

  9. 9.

    Paszek, M. J. & Weaver, V. M. The tension mounts: mechanics meets morphogenesis and malignancy. J. Mammary Gland Biol. Neoplasia 9, 325–342 (2004).

  10. 10.

    Plotnikov, S. V., Pasapera, A. M., Sabass, B. & Waterman, C. M. Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration. Cell 151, 1513–1527 (2012).

  11. 11.

    Hoffman, B. D., Grashoff, C. & Schwartz, M. A. Dynamic molecular processes mediate cellular mechanotransduction. Nature 475, 316–323 (2011).

  12. 12.

    Tambe, D. T. et al. Collective cell guidance by cooperative intercellular forces. Nat. Mater. 10, 469–475 (2011).

  13. 13.

    Doyle, A. D., Carvajal, N., Jin, A., Matsumoto, K. & Yamada, K. M. Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions. Nat. Commun. 6, 8720 (2015).

  14. 14.

    Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

  15. 15.

    Park, J. S. et al. The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. Biomaterials 32, 3921–3930 (2011).

  16. 16.

    Wolf, K. et al. Collagen-based cell migration models in vitro and in vivo. Semin. Cell Dev. Biol. 20, 931–941 (2009).

  17. 17.

    Cicchi, R. et al. From molecular structure to tissue architecture: collagen organization probed by SHG microscopy. J. Biophotonics 6, 129–142 (2013).

  18. 18.

    Dondossola, E. et al. Examination of the foreign body response to biomaterials by nonlinear intravital microscopy. Nat. Biomed. Eng. 1, 0007 (2016).

  19. 19.

    Provenzano, P. P. et al. Collagen density promotes mammary tumor initiation and progression. BMC Med. 6, 11 (2008).

  20. 20.

    Ilina, O., Bakker, G.-J., Vasaturo, A., Hoffman, R. M. & Friedl, P. Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion. Phys. Biol. 8, 029501 (2011).

  21. 21.

    Weigelin, B., Bakker, G.-J. & Friedl, P. Intravital third harmonic generation microscopy of collective melanoma cell invasion. IntraVital 1, 32–43 (2012).

  22. 22.

    Grossman, M. et al. Tumor cell invasion can be blocked by modulators of collagen fibril alignment that control assembly of the extracellular matrix. Cancer Res. 76, 4249–4258 (2016).

  23. 23.

    Maytin, E. V. Hyaluronan: more than just a wrinkle filler. Glycobiology 26, 553–559 (2016).

  24. 24.

    Hu, X., Margadant, F., Yao, M. & Sheetz, M. Molecular stretching modulates mechanosensing pathways. Protein Sci. 26, 1337–1351 (2017).

  25. 25.

    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).

  26. 26.

    Ridley, A. J. Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 16, 522–529 (2006).

  27. 27.

    Beningo, K. A., Hamao, K., Dembo, M., Wang, Y. & Hosoya, H. Traction forces of fibroblasts are regulated by the Rho-dependent kinase but not by the myosin light chain kinase. Arch. Biochem. Biophys. 456, 224–231 (2006).

  28. 28.

    Elosegui-Artola, A. et al. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat. Cell Biol. 18, 540–548 (2016).

  29. 29.

    Blanchoin, L., Boujemaa-Paterski, R., Sykes, C. & Plastino, J. Actin dynamics, architecture, and mechanics in cell motility. Physiol. Rev. 94, 235–263 (2014).

  30. 30.

    Kronenberg, N. M. et al. Long-term imaging of cellular forces with high precision by elastic resonator interference stress microscopy. Nat. Cell Biol. 19, 864–872 (2017).

  31. 31.

    McClatchey, A. I. ERM proteins at a glance. J. Cell Sci. 127, 3199–3204 (2014).

  32. 32.

    Mellad, J. A., Warren, D. T. & Shanahan, C. M. Nesprins LINC the nucleus and cytoskeleton. Curr. Opin. Cell Biol. 23, 47–54 (2011).

  33. 33.

    Miyoshi, J. & Takai, Y. Molecular perspective on tight-junction assembly and epithelial polarity. Adv. Drug Deliv. Rev. 57, 815–855 (2005).

  34. 34.

    Case, L. B. & Waterman, C. M. Integration of actin dynamics and cell adhesion by a three-dimensional, mechanosensitive molecular clutch. Nat. Cell Biol. 17, 955–963 (2015).

  35. 35.

    Mitchison, T. & Kirschner, M. Cytoskeletal dynamics and nerve growth. Neuron 1, 761–772 (1988).

  36. 36.

    Ray, A. et al. Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration. Nat. Commun. 8, 14923 (2017).

  37. 37.

    Riveline, D. et al. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153, 1175–1185 (2001).

  38. 38.

    del Rio, A. et al. Stretching single talin rod molecules activates vinculin binding. Science 323, 638–641 (2009).

  39. 39.

    Gehler, S. et al. Filamin A–β1 integrin complex tunes epithelial cell response to matrix tension. Mol. Biol. Cell 20, 3224–3238 (2009).

  40. 40.

    Starke, J., Wehrle-Haller, B. & Friedl, P. Plasticity of the actin cytoskeleton in response to extracellular matrix nanostructure and dimensionality. Biochem. Soc. Trans. 42, 1356–1366 (2014).

  41. 41.

    Sun, X. et al. Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance. Proc. Natl Acad. Sci. USA 112, 12557–1562 (2015).

  42. 42.

    Hall, M. S. et al. Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs. Proc. Natl Acad. Sci. USA 113, 14043–14048 (2016).

  43. 43.

    Solon, J., Levental, I., Sengupta, K., Georges, P. C. & Janmey, P. A. Fibroblast adaptation and stiffness matching to soft elastic substrates. Biophys. J. 93, 4453–4461 (2007).

  44. 44.

    Moon, J. J. et al. Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction. J. Cell. Physiol. 203, 166–176 (2005).

  45. 45.

    Maruthamuthu, V., Sabass, B., Schwarz, U. S. & Gardel, M. L. Cell–ECM traction force modulates endogenous tension at cell–cell contacts. Proc. Natl Acad. Sci. USA 108, 4708–4713 (2011).

  46. 46.

    McGregor, A. L., Hsia, C. R. & Lammerding, J. Squish and squeeze — the nucleus as a physical barrier during migration in confined environments. Curr. Opin. Cell Biol. 40, 32–40 (2016).

  47. 47.

    Khatau, S. B. et al. A perinuclear actin cap regulates nuclear shape. Proc. Natl Acad. Sci. USA 106, 19017–19022 (2009).

  48. 48.

    Swift, J. et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341, 1240104 (2013).

  49. 49.

    Harada, T. et al. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J. Cell Biol. 204, 669–682 (2014).

  50. 50.

    Rowat, A. C. et al. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J. Biol. Chem. 288, 8610–8618 (2013).

  51. 51.

    Denais, C. M. et al. Nuclear envelope rupture and repair during cancer cell migration. Science 352, 353–358 (2016).

  52. 52.

    Derenyi, I., Julicher, F. & Prost, J. Formation and interaction of membrane tubes. Phys. Rev. Lett. 88, 238101 (2002).

  53. 53.

    Fischer-Friedrich, E., Hyman, A. A., Jülicher, F., Müller, D. J. & Helenius, J. Quantification of surface tension and internal pressure generated by single mitotic cells. Sci. Rep. 4, 6213 (2014).

  54. 54.

    Mueller, J. et al. Load adaptation of lamellipodial actin networks. Cell 171, 188–200 (2017).

  55. 55.

    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).

  56. 56.

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

  57. 57.

    Petrie, R. J., Gavara, N., Chadwick, R. S. & Yamada, K. M. Nonpolarized signaling reveals two distinct modes of 3D cell migration. J. Cell Biol. 197, 439–455 (2012).

  58. 58.

    Stroka, K. M. et al. Water permeation drives tumor cell migration in confined microenvironments. Cell 157, 611–623 (2014).

  59. 59.

    Petrie, R. J., Koo, H. & Yamada, K. M. Generation of compartmentalized pressure by a nuclear piston governs cell motility in a 3D matrix. Science 345, 1062–1065 (2014).

  60. 60.

    Lämmermann, T. & Sixt, M. Mechanical modes of ‘amoeboid’ cell migration. Curr. Opin. Cell Biol. 21, 636–644 (2009).

  61. 61.

    Álvarez-González, B. et al. Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration. Biophys. J. 108, 821–832 (2015).

  62. 62.

    Lämmermann, T. et al. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453, 51–55 (2008).

  63. 63.

    Yip, A. K., Chiam, K.-H. & Matsudaira, P. Traction stress analysis and modeling reveal that amoeboid migration in confined spaces is accompanied by expansive forces and requires the structural integrity of the membrane–cortex interactions. Integr. Biol. 7, 1196–1211 (2015).

  64. 64.

    Gjorevski, N., Piotrowski, A. S., Varner, V. D. & Nelson, C. M. Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices. Sci. Rep. 5, 11458 (2015).

  65. 65.

    van Helvert, S. & Friedl, P. Strain stiffening of fibrillar collagen during individual and collective cell migration identified by AFM nanoindentation. ACS Appl. Mater. Interfaces 8, 21946–21955 (2016).

  66. 66.

    Jannat, R. A., Dembo, M. & Hammer, D. A. Traction forces of neutrophils migrating on compliant substrates. Biophys. J. 101, 575–584 (2011).

  67. 67.

    Reinhart-King, C. A., Dembo, M. & Hammer, D. A. The dynamics and mechanics of endothelial cell spreading. Biophys. J. 89, 676–689 (2005).

  68. 68.

    Undyala, V. V. et al. The calpain small subunit regulates cell–substrate mechanical interactions during fibroblast migration. J. Cell Sci. 121, 3581–3588 (2008).

  69. 69.

    Renkawitz, J. et al. Adaptive force transmission in amoeboid cell migration. Nat. Cell Biol. 11, 1438–1443 (2009).

  70. 70.

    Sanz-Moreno, V. et al. Rac activation and inactivation control plasticity of tumor cell movement. Cell 135, 510–523 (2008).

  71. 71.

    Ehrbar, M. et al. Elucidating the role of matrix stiffness in 3D cell migration and remodeling. Biophys. J. 100, 284–293 (2011).

  72. 72.

    Hegerfeldt, Y., Tusch, M., Bröcker, E. B. & Friedl, P. Collective cell movement in primary melanoma explants: plasticity of cell–cell interaction, β1-integrin function, and migration strategies. Cancer Res. 62, 2125–2130 (2002).

  73. 73.

    Matthes, T. & Gruler, H. Analysis of cell locomotion. Contact guidance of human polymorphonuclear leukocytes. Eur. Biophys. J. 15, 343–357 (1988).

  74. 74.

    Kubow, K. E., Conrad, S. K. & Horwitz, A. R. Matrix microarchitecture and myosin II determine adhesion in 3D matrices. Curr. Biol. 23, 1607–1619 (2013).

  75. 75.

    Dickinson, R. B., Guido, S. & Tranquillo, R. T. Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels. Ann. Biomed. Eng. 22, 342–356 (1994).

  76. 76.

    Driscoll, M. K., Sun, X., Guven, C., Fourkas, J. T. & Losert, W. Cellular contact guidance through dynamic sensing of nanotopography. ACS Nano 8, 3546–3555 (2014).

  77. 77.

    Gopal, S. et al. Fibronectin-guided migration of carcinoma collectives. Nat. Commun. 8, 14105 (2017).

  78. 78.

    Kubow, K. E., Shuklis, V. D., Sales, D. J. & Horwitz, A. R. Contact guidance persists under myosin inhibition due to the local alignment of adhesions and individual protrusions. Sci. Rep. 7, 14380 (2017).

  79. 79.

    Wolf, K., Müller, R., Borgmann, S., Bröcker, E. B. & Friedl, P. Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. Blood 102, 3262–3269 (2003).

  80. 80.

    Haeger, A., Krause, M., Wolf, K. & Friedl, P. Cell jamming: collective invasion of mesenchymal tumor cells imposed by tissue confinement. Biochim. Biophys. Acta 1840, 2386–2395 (2014).

  81. 81.

    Nam, K.-H. et al. Multiscale cues drive collective cell migration. Sci. Rep. 6, 29749 (2016).

  82. 82.

    Lo, C. M., Wang, H. B., Dembo, M. & Wang, Y. L. Cell movement is guided by the rigidity of the substrate. Biophys. J. 79, 144–152 (2000).

  83. 83.

    Vincent, L. G., Choi, Y. S., Alonso-Latorre, B., del Álamo, J. C. & Engler, A. J. Mesenchymal stem cell durotaxis depends on substrate stiffness gradient strength. Biotechnol. J. 8, 472–484 (2013).

  84. 84.

    Sunyer, R. et al. Collective cell durotaxis emerges from long-range intercellular force transmission. Science 353, 1157–1161 (2016).

  85. 85.

    Elosegui-Artola, A. et al. Rigidity sensing and adaptation through regulation of integrin types. Nat. Mater. 13, 631–637 (2014).

  86. 86.

    Paszek, M. J., Boettiger, D., Weaver, V. M. & Hammer, D. A. Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput. Biol. 5, e1000604 (2009).

  87. 87.

    Weber, M. et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science 339, 328–332 (2013).

  88. 88.

    McCarthy, J. B. & Furcht, L. T. Laminin and fibronectin promote the haptotactic migration of B16 mouse melanoma cells in vitro. J. Cell Biol. 98, 1474–1480 (1984).

  89. 89.

    Johnson, H. E. et al. F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling. J. Cell Biol. 208, 443–455 (2015).

  90. 90.

    Wu, C. et al. Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis. Cell 148, 973–987 (2012).

  91. 91.

    Autenrieth, T. J. et al. Actomyosin contractility and RhoGTPases affect cell-polarity and directional migration during haptotaxis. Integr. Biol. 8, 1067–1078 (2016).

  92. 92.

    Painter, K. J. Modelling cell migration strategies in the extracellular matrix. J. Math. Biol. 58, 511–543 (2009).

  93. 93.

    Schlüter, D. K. & Ramis-Conde, I. & Chaplain, M. A. J. Computational modeling of single-cell migration: the leading role of extracellular matrix fibers. Biophys. J. 103, 1141–1151 (2012).

  94. 94.

    Schwarz, U. S. & Safran, S. A. Physics of adherent cells. Rev. Mod. Phys. 85, 1327 (2013).

  95. 95.

    Mogilner, A. & Keren, K. The shape of motile cells. Curr. Biol. 19, R762–R771 (2009).

  96. 96.

    Novikova, E. A., Raab, M., Discher, D. E. & Storm, C. Persistence-driven durotaxis: generic, directed motility in rigidity gradients. Phys. Rev. Lett. 118, 078103 (2015).

  97. 97.

    He, X. & Jiang, Y. Substrate curvature regulates cell migration. Phys. Biol. 14, 35006 (2017).

  98. 98.

    Szabó, A. & Merks, R. M. H. Cellular Potts modeling of tumor growth, tumor invasion, and tumor evolution. Front. Oncol. 3, 87 (2013).

  99. 99.

    van Hecke, M. Jamming of soft particles: geometry, mechanics, scaling and isostaticity. J. Phys. Condens. Matter 22, 033101 (2010).

  100. 100.

    Bi, D., Lopez, J. H., Schwarz, J. M. & Manning, M. L. A density-independent rigidity transition in biological tissues. Nat. Phys. 11, 1074–1079 (2015).

  101. 101.

    Park, J.-A. et al. Unjamming and cell shape in the asthmatic airway epithelium. Nat. Mater. 14, 1040–1048 (2015).

  102. 102.

    Scianna, M., Preziosi, L. & Wolf, K. A cellular Potts model simulating cell migration on and in matrix environments. Math. Biosci. Eng. 10, 235–261 (2013).

  103. 103.

    Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005).

  104. 104.

    Schneider, K. R. Britton, N. F.: Reaction-diffusion equations and their application to biology. Academic Press, London 1986, 277 S., $ 65.–. Biometrical J. 31, 720 (1989).

  105. 105.

    Paszek, M. J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254 (2005).

  106. 106.

    Carey, S. P. et al. Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK. Integr. Biol. 8, 821–835 (2016).

  107. 107.

    Oudin, M. J. et al. Tumor cell-driven extracellular matrix remodeling drives haptotaxis during metastatic progression. Cancer Discov. 6, 516–531 (2016).

  108. 108.

    Page-McCaw, A., Ewald, A. J. & Werb, Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell Biol. 8, 221–233 (2007).

  109. 109.

    Cox, T. R. & Erler, J. T. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Dis. Model. Mech. 4, 165–178 (2011).

  110. 110.

    Kim, J. et al. Stress-induced plasticity of dynamic collagen networks. Nat. Commun. 8, 842 (2017).

  111. 111.

    Wolf, K. et al. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J. Cell Biol. 201, 1069–1084 (2013).

  112. 112.

    Wolf, K. et al. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat. Cell Biol. 9, 893–904 (2007).

  113. 113.

    Kirmse, R., Otto, H. & Ludwig, T. Interdependency of cell adhesion, force generation and extracellular proteolysis in matrix remodeling. J. Cell Sci. 124, 1857–1866 (2011).

  114. 114.

    Stratman, A. N. et al. Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices. Blood 114, 237–247 (2009).

  115. 115.

    Kelley, L. C., Lohmer, L. L., Hagedorn, E. J. & Sherwood, D. R. Traversing the basement membrane in vivo: a diversity of strategies. J. Cell Biol. 204, 291–302 (2014).

  116. 116.

    Glentis, A. et al. Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane. Nat. Commun. 8, 924 (2017).

  117. 117.

    Seano, G. et al. Endothelial podosome rosettes regulate vascular branching in tumour angiogenesis. Nat. Cell Biol. 16, 931–941 (2014).

  118. 118.

    Levental, K. R. et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139, 891–906 (2009).

  119. 119.

    Sawada, Y. et al. Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell 127, 1015–1026 (2006).

  120. 120.

    Kong, F., Garcia, A. J., Mould, A. P., Humphries, M. J. & Zhu, C. Demonstration of catch bonds between an integrin and its ligand. J. Cell Biol. 185, 1275–1284 (2009).

  121. 121.

    Guo, B. & Guilford, W. H. Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction. Proc. Natl Acad. Sci. USA 103, 9844–9849 (2006).

  122. 122.

    Buckley, C. D. et al. The minimal cadherin–catenin complex binds to actin filaments under force. Science 346, 1254211 (2014).

  123. 123.

    Klotzsch, E. et al. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc. Natl Acad. Sci. USA 106, 18267–18272 (2009).

  124. 124.

    Dong, X. et al. Force interacts with macromolecular structure in activation of TGF-β. Nature 542, 55–59 (2017).

  125. 125.

    Buscemi, L. et al. The single-molecule mechanics of the latent TGF-β1 complex. Curr. Biol. 21, 2046–2054 (2011).

  126. 126.

    Klingberg, F. et al. Prestress in the extracellular matrix sensitizes latent TGF-β1 for activation. J. Cell Biol. 207, 283–297 (2014).

  127. 127.

    Carmeliet, P. & Jain, R. K. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298–307 (2011).

  128. 128.

    Hinz, B. The role of myofibroblasts in wound healing. Curr. Res. Transl. Med. 64, 171–177 (2016).

  129. 129.

    Hotary, K. B. et al. Matrix metalloproteinases (MMPs) regulate fibrin-invasive activity via MT1-MMP-dependent and -independent processes. J. Exp. Med. 195, 295–308 (2002).

  130. 130.

    Koivisto, L., Heino, J., Häkkinen, L. & Larjava, H. Integrins in wound healing. Adv. Wound Care 3, 762–783 (2014).

  131. 131.

    Mohammadi, H. et al. Filamin A mediates wound closure by promoting elastic deformation and maintenance of tension in the collagen matrix. J. Invest. Dermatol. 135, 2852–2861 (2015).

  132. 132.

    Laurens, N. et al. Single and combined effects of αvβ3- and α5β1-integrins on capillary tube formation in a human fibrinous matrix. Angiogenesis 12, 275–285 (2009).

  133. 133.

    Du, Y. et al. Three-dimensional characterization of mechanical interactions between endothelial cells and extracellular matrix during angiogenic sprouting. Sci. Rep. 6, 21362 (2016).

  134. 134.

    Yana, I. et al. Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells. J. Cell Sci. 120, 1607–1614 (2007).

  135. 135.

    Stratman, A. N., Malotte, K. M., Mahan, R. D., Davis, M. J. & Davis, G. E. Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood 114, 5091–5101 (2009).

  136. 136.

    Lan, T. H., Huang, X. Q. & Tan, H. M. Vascular fibrosis in atherosclerosis. Cardiovasc. Pathol. 22, 401–407 (2013).

  137. 137.

    Oliveira, C. L. N., Bates, J. H. T. & Suki, B. A network model of correlated growth of tissue stiffening in pulmonary fibrosis. New J. Phys. 16, 065022 (2014).

  138. 138.

    Sutcliffe, J. E. S. et al. Changes in the extracellular matrix surrounding human chronic wounds revealed by 2-photon imaging. Int. Wound J. 141225–1236 (2017).

  139. 139.

    Odenthal, J., Takes, R. & Friedl, P. Plasticity of tumor cell invasion: governance by growth factors and cytokines. Carcinogenesis 37, 1117–1128 (2016).

  140. 140.

    Alexander, N. R. et al. Extracellular matrix rigidity promotes invadopodia activity. Curr. Biol. 18, 1295–1299 (2008).

  141. 141.

    Chang, T. T., Thakar, D. & Weaver, V. M. Force-dependent breaching of the basement membrane. Matrix Biol. 57–58, 178–189 (2017).

  142. 142.

    Goetz, J. G. et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 146, 148–163 (2011).

  143. 143.

    Gaggioli, C. et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat. Cell Biol. 9, 1392–1400 (2007).

  144. 144.

    Loeffler, M., Krüger, J. A., Niethammer, A. G. & Reisfeld, R. A. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J. Clin. Invest. 116, 1955–1962 (2006).

  145. 145.

    Nia, H. T. et al. Solid stress and elastic energy as measures of tumour mechanopathology. Nat. Biomed. Eng. 1, 0004 (2016).

  146. 146.

    Ahmadzadeh, H. et al. Modeling the two-way feedback between contractility and matrix realignment reveals a nonlinear mode of cancer cell invasion. Proc. Natl Acad. Sci. USA 114, E1617–E1626 (2017).

  147. 147.

    Barriga, E., Franze, K., Charras, G. & Mayor, R. How mechanics orchestrate morphogenesis: mesodermal stiffening triggers neural crest migration in vivo. Mech. Dev. 145, S46 (2017).

  148. 148.

    Vennin, C. et al. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci. Transl. Med. 9, eaai8504 (2017).

  149. 149.

    Miroshnikova, Y. A., Nava, M. M. & Wickstrom, S. A. Emerging roles of mechanical forces in chromatin regulation. J. Cell Sci. 130, 2243–2250 (2017).

  150. 150.

    Sadok, A. et al. Rho kinase inhibitors block melanoma cell migration and inhibit metastasis. Cancer Res. 75, 2272–2284 (2015).

  151. 151.

    Hirata, E. et al. Intravital imaging reveals how BRAF inhibition generates drug-tolerant microenvironments with high integrin β1/FAK signaling. Cancer Cell 27, 574–588 (2015).

  152. 152.

    Nilsson, M., Adamo, H., Bergh, A. & Halin Bergström, S. Inhibition of lysyl oxidase and lysyl oxidase-like enzymes has tumour-promoting and tumour-suppressing roles in experimental prostate cancer. Sci. Rep. 6, 19608 (2016).

  153. 153.

    Couppé, C. et al. Mechanical properties and collagen cross-linking of the patellar tendon in old and young men. J. Appl. Physiol. 107, 880–886 (2009).

  154. 154.

    Halfter, W. et al. New concepts in basement membrane biology. FEBS J. 282, 4466–4479 (2015).

  155. 155.

    Zioupos, P. & Currey, J. Changes in the stiffness, strength, and toughness of human cortical bone with age. Bone 22, 57–66 (1998).

  156. 156.

    Marshall, B. T. et al. Direct observation of catch bonds involving cell-adhesion molecules. Nature 423, 190–193 (2003).

  157. 157.

    Cluzel, C. et al. The mechanisms and dynamics of αvβ3 integrin clustering in living cells. J. Cell Biol. 171, 383–392 (2005).

  158. 158.

    Sabeh, F., Shimizu-Hirota, R. & Weiss, S. J. Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J. Cell Biol. 185, 11–19 (2009).

  159. 159.

    Meehan, S. & Nain, A. S. Role of suspended fiber structural stiffness and curvature on single-cell migration, nucleus shape, and focal-adhesion-cluster length. Biophys. J. 107, 2604–2611 (2014).

  160. 160.

    Holmes, D. F. et al. Corneal collagen fibril structure in three dimensions: structural insights into fibril assembly, mechanical properties, and tissue organization. Proc. Natl Acad. Sci. USA 98, 7307–7312 (2001).

  161. 161.

    Liliensiek, S. J., Nealey, P. & Murphy, C. J. Characterization of endothelial basement membrane nanotopography in rhesus macaque as a guide for vessel tissue engineering. Tissue Eng. Part A 15, 2643–2651 (2009).

  162. 162.

    Pot, S. A. et al. Nanoscale topography-induced modulation of fundamental cell behaviors of rabbit corneal keratocytes, fibroblasts, and myofibroblasts. Investig. Ophthalmol. Vis. Sci. 51, 1373–1381 (2010).

  163. 163.

    Nelson, C. M. et al. Emergent patterns of growth controlled by multicellular form and mechanics. Proc. Natl Acad. Sci. USA 102, 11594–11599 (2005).

  164. 164.

    Hatami-Marbini, H., Etebu, E. & Rahimi, A. Swelling pressure and hydration behavior of porcine corneal stroma. Curr. Eye Res. 38, 1124–1132 (2013).

  165. 165.

    Majno, G., Palade, G. E. & Schoefl, G. I. Studies on inflammation. II. the site of action of histamine and serotonin along the vascular tree: a topographic study. J. Biophys. Biochem. Cytol. 11, 607–626 (1961).

  166. 166.

    Weninger, W., Biro, M. & Jain, R. Leukocyte migration in the interstitial space of non-lymphoid organs. Nat. Rev. Immunol. 14, 232–246 (2014).

  167. 167.

    Shields, J. D. et al. Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Cancer Cell 11, 526–538 (2007).

  168. 168.

    Ingber, D. E., Wang, N. & Stamenović, D. Tensegrity, cellular biophysics, and the mechanics of living systems. Rep. Prog. Phys. 77, 46603 (2014).

  169. 169.

    Swaminathan, V. et al. Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res. 71, 5075–5080 (2011).

  170. 170.

    Broedersz, C. P. & MacKintosh, F. C. Modeling semiflexible polymer networks. Rev. Mod. Phys. 86, 995 (2014).

  171. 171.

    Bischofs, I. B. & Schwarz, U. S. Cell organization in soft media due to active mechanosensing. Proc. Natl Acad. Sci. USA 100, 9274–9279 (2003).

  172. 172.

    Kim, M. C., Whisler, J., Silberberg, Y. R., Kamm, R. D. & Asada, H. H. Cell Invasion dynamics into a three dimensional extracellular matrix fibre network. PLoS Comput. Biol. 11, e1004535 (2015).

  173. 173.

    MacKintosh, F. C., Käs, J. & Janmey, P. A. Elasticity of semiflexible biopolymer networks. Phys. Rev. Lett. 75, 4425–4428 (1995).

  174. 174.

    Gardel, M. L. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004).

  175. 175.

    Mofrad, M. R. K. & Kamm, R. D. (eds) Cytoskeletal Mechanics: Models and Measurements in Cell Mechanics Ch. 8 (Cambridge Univ. Press, Cambridge, 2006).

  176. 176.

    Preziosi, L. & Vitale, G. A multiphase model of tumor and tissue growth including cell adhesion and plastic reorganization. Math. Model. Methods Appl. Sci. 21, 1901–1932 (2011).

  177. 177.

    Ribeiro, F. O., Gómez-Benito, M. J., Folgado, J., Fernandes, P. R. & García-Aznar, J. M. Computational model of mesenchymal migration in 3D under chemotaxis. Comput. Methods Biomech. Biomed. Engin. 20, 59–74 (2017).

  178. 178.

    Chauvière, A., Preziosi, L. & Verdier, C. Cell Mechanics: from Single Scale-Based Models to Multiscale Modeling (CRC Press, Boca Raton, 2010).

  179. 179.

    van Oers, R. F. M., Rens, E. G., LaValley, D. J., Reinhart-King, C. A. & Merks, R. M. H. Mechanical cell-matrix feedback explains pairwise and collective endothelial cell behavior in vitro. PLoS Comput. Biol. 10, e1003774 (2014).

Download references

Acknowledgements

We thank M. Zegers for proofreading the manuscript. The P.F. laboratory is supported by the European Research Council (617430-DEEPINSIGHT), NWO-Vici (918.11.626), Horizon 2020 consortium MULTIMOT (634107-2), the Cancer Genomics Center, (CGC.nl), NIH-U54 CA210184-01, the MD Anderson Cancer Center Moon Shot program and the Radboud Nanomedicine Alliance. C.S. was supported by funds from NWO-FOM (E1012M, E1009M, E1013M) and the TU/e Institute for Complex Molecular Systems.

Author information

Affiliations

  1. Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    • Sjoerd van Helvert
    •  & Peter Friedl
  2. Department of Applied Physics and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands

    • Cornelis Storm
  3. David H. Koch Center for Applied Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Peter Friedl
  4. Cancer Genomics Center, Utrecht, The Netherlands

    • Peter Friedl

Authors

  1. Search for Sjoerd van Helvert in:

  2. Search for Cornelis Storm in:

  3. Search for Peter Friedl in:

Contributions

All authors prepared the figures and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Peter Friedl.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/s41556-017-0012-0