The physics of cancer: the role of physical interactions and mechanical forces in metastasis

Abstract

Metastasis is a complex, multistep process responsible for >90% of cancer-related deaths. In addition to genetic and external environmental factors, the physical interactions of cancer cells with their microenvironment, as well as their modulation by mechanical forces, are key determinants of the metastatic process. We reconstruct the metastatic process and describe the importance of key physical and mechanical processes at each step of the cascade. The emerging insight into these physical interactions may help to solve some long-standing questions in disease progression and may lead to new approaches to developing cancer diagnostics and therapies.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The metastatic process.
Figure 2: The physics of invasion and intravasation.
Figure 3: Arrest of circulating tumour cells.
Figure 4: Capture and arrest of circulating tumour cells.

References

  1. 1

    Chambers, A. F., Groom, A. C. & MacDonald, I. C. Dissemination and growth of cancer cells in metastatic sites. Nature Rev. Cancer 2, 563–572 (2002).

    CAS  Google Scholar 

  2. 2

    Steeg, P. S. Tumor metastasis: mechanistic insights and clinical challenges. Nature Med. 12, 895–904 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Kalluri, R. & Weinberg, R. A. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420–1428 (2009).

    CAS  Google Scholar 

  4. 4

    Chaffer, C. L. & Weinberg, R. A. A perspective on cancer cellmetastasis. Science 331, 1559–1564 (2011).

    CAS  PubMed  Google Scholar 

  5. 5

    Thiery, J. P. & Sleeman, J. P. Complex networks orchestrate epithelial-mesenchymal transitions. Nature Rev. Mol. Cell Biol. 7, 131–142 (2006).

    CAS  Google Scholar 

  6. 6

    Polyak, K. & Weinberg, R. A. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nature Rev. Cancer 9, 265–273 (2009).

    CAS  Google Scholar 

  7. 7

    Hotary, K., Li, X. Y., Allen, E., Stevens, S. L. & Weiss, S. J. A cancer cell metalloprotease triad regulates the basement membrane transmigration program. Genes Dev. 20, 2673–2686 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Hotary, K. B., Allen, E. D., Brooks, P. C., Datta, N. S., Long, M. W. & Weiss, S. J. Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114, 33–45 (2003).

    CAS  Google Scholar 

  9. 9

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

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    De Wever, O., Demetter, P., Mareel, M. & Bracke, M. Stromal myofibroblasts are drivers of invasive cancer growth. Int. J. Cancer 123, 2229–2238 (2008).

    CAS  PubMed  Google Scholar 

  11. 11

    Provenzano, P. P., Inman, D. R., Eliceiri, K. W. & Keely, P. J. Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage. Oncogene 28, 4326–4343 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science 302, 1704–1709 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).

    CAS  PubMed  Google Scholar 

  14. 14

    Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359–369 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Fraley, S. I. et al. A distinctive role for focal adhesion proteins in three-dimensional cell motility. Nature Cell Biol. 12, 598–604 (2010).

    CAS  Google Scholar 

  17. 17

    Zaman, M. H. et al. Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis. Proc. Natl Acad. Sci. USA 103, 10889–10894 (2006).

    CAS  Google Scholar 

  18. 18

    Wozniak, M. A., Desai, R., Solski, P. A., Der, C. J. & Keely, P. J. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J. Cell Biol. 163, 583–595 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Yamazaki, D., Kurisu, S. & Takenawa, T. Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates. Oncogene 28, 1570–1583 (2009).

    CAS  PubMed  Google Scholar 

  20. 20

    Doyle, A. D., Wang, F. W., Matsumoto, K. & Yamada, K. M. One-dimensional topography underlies three-dimensional fibrillar cell migration. J. Cell Biol. 184, 481–490 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Geiger, B., Spatz, J. P. & Bershadsky, A. D. Environmental sensing through focal adhesions. Nature Rev. Mol. Cell Biol. 10, 21–33 (2009).

    CAS  Google Scholar 

  22. 22

    Wehrle-Haller, B. & Imhof, B. The inner lives of focal adhesions. Trends Cell Biol. 12, 382–389 (2002).

    CAS  PubMed  Google Scholar 

  23. 23

    Parsons, J. T., Horwitz, A. R. & Schwartz, M. A. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature Rev. Mol. Cell Biol. 11, 633–643 (2010).

    CAS  Google Scholar 

  24. 24

    Smith, M. L. et al. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol. 5, e268 (2007).

    PubMed  PubMed Central  Google Scholar 

  25. 25

    Sun, S. X., Walcott, S. & Wolgemuth, C. W. Cytoskeletal cross-linking and bundling in motor-independent contraction. Curr. Biol. 20, R649–R654 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Bloom, R. J., George, J. P., Celedon, A., Sun, S. X. & Wirtz, D. Mapping local matrix remodeling induced by a migrating tumor cell using three-dimensional multiple-particle tracking. Biophys. J. 95, 4077–4088 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Shih, W. T. & Yamada, S. Myosin IIA dependent retrograde flow drives 3D cellmigration. Biophys. J. 98, L29–L31 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Beningo, K. A., Dembo, M., Kaverina, I., Small, J. V. & Wang, Y. L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153, 881–888 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Legant, W. R., Miller, J. S., Blakely, B. L., Cohen, D. M., Genin, G. M. & Chen, C. S. Measurement of mechanical tractions exerted by cells in three-dimensional matrices. Nature Methods 7, 969–971 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Ellsmere, J. C., Khanna, R. A. & Lee, J. M. Mechanical loading of bovine pericardium accelerates enzymatic degradation. Biomaterials 20, 1143–1150 (1999).

    CAS  PubMed  Google Scholar 

  31. 31

    Beerling, E., Ritsma, L., Vrisekoop, N., Derksen, P. W. & van Rheenen, J. Intravital microscopy: new insights into metastasis of tumors. J. Cell Sci. 124, 299–310 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

    Sahai, E., Wyckoff, J., Philippar, U., Segall, J. E., Gertler, F. & Condeelis, J. Simultaneous imaging of, GFP, CFP and collagen in tumors in vivo using multiphoton microscopy. BMC Biotechnol. 5, 14 (2005).

    PubMed  PubMed Central  Google Scholar 

  33. 33

    Giampieri, S. et al. Localized and reversible TGF-β signalling switches breast cancer cells from cohesive to single cell motility. Nature Cell Biol. 11, 1287–1296 (2009).

    CAS  PubMed  Google Scholar 

  34. 34

    Hidalgo-Carcedo, C. et al. Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nature Cell Biol. 13, 49–58 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Kurisu, S. & Takenawa, T. WASP and WAVE family proteins: friends or foes in cancer invasion? Cancer Sci. 101, 2093–2104 (2010).

    CAS  PubMed  Google Scholar 

  36. 36

    Iwaya, K., Norio, K. & Mukai, K. Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma. Mod. Pathol. 20, 339–343 (2007).

    CAS  PubMed  Google Scholar 

  37. 37

    Yoder, B. J. et al. The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course. Clin. Cancer Res. 11, 186–192 (2005).

    CAS  PubMed  Google Scholar 

  38. 38

    Li, J. et al. PTEN, a putative protein tyrosine phosphotase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943–1947 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Iijima, M. & Devreotes, P. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599–610 (2002).

    CAS  PubMed  Google Scholar 

  40. 40

    Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 318, 1108–1113 (2007).

    CAS  Google Scholar 

  41. 41

    Sahai, E. & Marshall, C. J. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biol. 5, 711–719 (2003).

    CAS  Google Scholar 

  42. 42

    Sounni, N. E. et al. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. FASEB J. 16, 555–564 (2002).

    CAS  PubMed  Google Scholar 

  43. 43

    Adhikari, A. S., Chai, J. & Dunn, A. R. Mechanical load induces a 100-fold increase in the rate of collagen proteolysis by MMP-1. J. Am. Chem. Soc. 133, 1686–1689 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Kumar, S. & Weaver, V. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 28, 113–127 (2009).

    PubMed  PubMed Central  Google Scholar 

  45. 45

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

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Provenzano, P. P., Inman, D. R., Eliceiri, K. W., Trier, S. M. & Keely, P. J. Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization. Biophys. J. 95, 5374–5384 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Wirtz, D. Particle-tracking microrheology of living cells: principles and applications. Annu. Rev. Biophys. 38, 301–326 (2009).

    CAS  PubMed  Google Scholar 

  48. 48

    Friedl, P., Wolf, K. & Lammerding, J. Nuclear mechanics during cell migration. Curr. Opin. Cell Biol. 23, 1–10 (2010).

    Google Scholar 

  49. 49

    Dahl, K. N., Kahn, S. M., Wilson, K. L. & Discher, D. E. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J. Cell Sci. 117, 4779–4786 (2004).

    CAS  PubMed  Google Scholar 

  50. 50

    Tseng, Y., Lee, J. S., Kole, T. P., Jiang, I. & Wirtz, D. Micro-organization and visco-elasticity of the interphase nucleus revealed by particle nanotracking. J. Cell Sci. 117, 2159–2167 (2004).

    CAS  PubMed  Google Scholar 

  51. 51

    Gerlitz, G. & Bustin, M. Efficient cell migration requires global chromatin condensation. J. Cell Sci. 123, 2207–2217 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Crisp, M. et al. Coupling of the nucleus and cytoplasm: role of the LINC complex. J. Cell Biol. 172, 41–53 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Stewart-Hutchinson, P. J., Hale, C. M., Wirtz, D. & Hodzic, D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp. Cell Res. 314, 1892–1905 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Hale, C. M. et al. Dysfunctional connections between the nucleus and the actin and microtubule networks in laminopathic models. Biophys. J. 95, 5462–5475 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Lee, J. S. et al. Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. Biophys. J. 93, 2542–2552 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Starr, D. A. & Han, M. ANChors away: an actin based mechanism of nuclear positioning. J. Cell Sci. 116, 211–216 (2003).

    CAS  PubMed  Google Scholar 

  57. 57

    Starr, D. A. et al. unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration. Development 128, 5039–5050 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58

    Technau, M. & Roth, S. The Drosophila KASH domain proteins Msp-300 and Klarsicht and the SUN domain protein klaroid have no essential function during oogenesis. Fly (Austin) 2, 82–91 (2008).

    Google Scholar 

  59. 59

    Lammerding, J. et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113, 370–378 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Cross, S. E., Jin, Y. S., Rao, J. & Gimzewski, J. K. Nanomechanical analysis of cells from cancer patients. Nature Nanotech. 2, 780–783 (2007).

    CAS  Google Scholar 

  61. 61

    Guck, J. et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88, 3689–3698 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Yeung, T. et al. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil. Cytoskeleton 60, 24–34 (2005).

    PubMed  Google Scholar 

  63. 63

    Panorchan, P., Lee, J. S., Kole, T. P., Tseng, Y. & Wirtz, D. Microrheology and ROCK signaling of human endothelial cells embedded in a 3D matrix. Biophys. J. 91, 3499–3507 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Baker, E. L., Bonnecaze, R. T. & Zaman, M. H. Extracellular matrix stiffness and architecture govern intracellular rheology in cancer. Biophys. J. 97, 1013–1021 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Baker, E. L., Lu, J., Yu, D. H., Bonnecaze, R. T. & Zaman, M. H. Cancer cell stiffness: integrated roles of three-dimensional matrix stiffness and transforming potential. Biophys. J. 99, 2048–2057 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Lee, J. S. et al. Ballistic intracellular nanorheology reveals ROCK-hard cytoplasmic stiffening response to fluid flow. J. Cell Sci. 119, 1760–1768 (2006).

    CAS  PubMed  Google Scholar 

  67. 67

    Swartz, M. A. & Fleury, M. E. Interstitial flow and its effects in soft tissues. Annu. Rev. Biomed. Eng. 9, 229–256 (2007).

    CAS  PubMed  Google Scholar 

  68. 68

    Mycielska, M. E. & Djamgoz, M. B. A. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J. Cell Sci. 117, 1631–1639 (2004).

    CAS  PubMed  Google Scholar 

  69. 69

    Fidler, I. J., Yano, S., Zhang, R. D., Fujimaki, T. & Bucana, C. D. The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol. 3, 53–57 (2002).

    CAS  Google Scholar 

  70. 70

    Turitto, V. T. Blood viscosity, mass transport, and thrombogenesis. Prog. Hemost. Thromb. 6, 139–177 (1982).

    CAS  PubMed  Google Scholar 

  71. 71

    Weinbaum, S., Cowin, S. C. & Zeng, Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27, 339–360 (1994).

    CAS  PubMed  Google Scholar 

  72. 72

    Weinbaum, S., Duan, Y., Satlin, L. M., Wang, T. & Weinstein, A. M. Mechanotransduction in the renal tubule. Am. J. Physiol. Renal Physiol. 299, F1220–F1236 (2010).

    Google Scholar 

  73. 73

    Kienast, Y. et al. Real-time imaging reveals the single steps of brain metastasis formation. Nature Med. 16, 116–122 (2010).

    CAS  PubMed  Google Scholar 

  74. 74

    Zhu, C., Yago, T., Lou, J. Z., Zarnitsyna, V. I. & McEver, R. P. Mechanisms for flow-enhanced cell adhesion. Ann. Biomed. Eng. 36, 604–621 (2008).

    PubMed  PubMed Central  Google Scholar 

  75. 75

    Chang, K. C. & Hammer, D. A. The forward rate of binding of surface-tethered reactants: effect of relative motion between two surfaces. Biophys. J. 76, 1280–1292 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Duguay, D., Foty, R. A. & Steinberg, M. S. Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev. Biol. 253, 309–323 (2003).

    CAS  PubMed  Google Scholar 

  77. 77

    Niessen, C. M. & Gumbiner, B. M. Cadherin-mediated cell sorting not determined by binding or adhesion specificity. J. Cell Biol. 156, 389–399 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Huang, J. et al. The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness. Nature 464, 932–936 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Marshall, B. T., Long, M., Piper, J. W., Yago, T., McEver, R. P. & Zhu, C. Direct observation of catch bonds involving cell-adhesion molecules. Nature 423, 190–193 (2003).

    CAS  PubMed  Google Scholar 

  80. 80

    Hynes, R. O. Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Lorger, M., Krueger, J. S., O'Neal, M., Staflin, K. & Felding-Habermann, B. Activation of tumor cell integrin αvβ3 controls angiogenesis and metastatic growth in the brain. Proc. Natl Acad. Sci. USA 106, 10666–10671 (2009).

    CAS  Google Scholar 

  82. 82

    Gasic, G. J., Gasic, T. B. & Stewart, C. C. Antimetastatic effects associated with platelet reduction. Proc. Natl Acad. Sci. USA 61, 46–52 (1968).

    CAS  PubMed  Google Scholar 

  83. 83

    Camerer, E. et al. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 104, 397–401 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Karpatkin, S., Pearlstein, E., Ambrogio, C. & Coller, B. S. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J. Clin. Invest. 81, 1012–1019 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Nieswandt, B., Hafner, M., Echtenacher, B. & Mannel, D. N. Lysis of tumor cells by natutal killer cells in mice is impeded by platelets. Cancer Res. 59, 1295–1300 (1999).

    CAS  PubMed  Google Scholar 

  86. 86

    Palumbo, J. S. et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105, 178–185 (2005).

    CAS  PubMed  Google Scholar 

  87. 87

    Burdick, M. M. & Konstantopoulos, K. Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow. Am. J. Physiol. Cell Physiol. 287, C539–C547 (2004).

    CAS  PubMed  Google Scholar 

  88. 88

    Felding-Habermann, B., Habermann, R., Salvidar, E. & Ruggeri, Z. M. Role of β3 integrins in melanoma cell adhesion to activated platelets under flow. J. Biol. Chem. 271, 5892–5900 (1996).

    CAS  PubMed  Google Scholar 

  89. 89

    Gay, L. J. & Felding-Habermann, B. Contribution of platelets to tumour metastasis. Nature Rev. Cancer 11, 123–134 (2011).

    CAS  Google Scholar 

  90. 90

    Nash, G., Turner, L., Scully, M. & Kakkar, A. Platelets and cancer. Lancet Oncol. 3, 425–430 (2002).

    CAS  PubMed  Google Scholar 

  91. 91

    Pinedo, H. M., Verheul, H. M., D'Amato, R. J. & Folkman, J. Involvement of platelets in tumour angiogenesis? Lancet 352, 1775–1777 (1998).

    CAS  PubMed  Google Scholar 

  92. 92

    Crissman, J. D., Hatfield, J., Schaldenbrand, M., Sloane, B. F. & Honn, K. V. Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study. Lab. Invest. 53, 470–478 (1985).

    CAS  PubMed  Google Scholar 

  93. 93

    Burdick, M. M., McCaffery, J. M., Kim, Y. S., Bochner, B. S. & Konstantopoulos, K. Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow. Am. J. Physiol. Cell Physiol. 284, C977–C987 (2003).

    CAS  PubMed  Google Scholar 

  94. 94

    Borsig, L. et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc. Natl Acad. Sci. USA 98, 3352–3357 (2001).

    CAS  PubMed  Google Scholar 

  95. 95

    Borsig, L., Wong, R., Hynes, R. O., Varki, N. M. & Varki, A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc. Natl Acad. Sci. USA 99, 2193–2198 (2002).

    CAS  PubMed  Google Scholar 

  96. 96

    Jadhav, S., Bochner, B. S. & Konstantopoulos, K. Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte – colon carcinoma cell adhesive interactions. J. Immunol. 167, 5986–5993 (2001).

    CAS  PubMed  Google Scholar 

  97. 97

    McCarty, O. J. T., Mousa, S. A., Bray, P. F. & Konstantopoulos, K. Immobilized platelets support human colon carcinoma cell tethering, rolling and firm adhesion under dynamic flow conditions. Blood 96, 1789–1797 (2000).

    CAS  PubMed  Google Scholar 

  98. 98

    Laubli, H., Stevenson, J. L., Varki, A., Varki, N. M. & Borsig, L. L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res. 66, 1536–1542 (2006).

    PubMed  Google Scholar 

  99. 99

    Biancone, L., Araki, M., Araki, K., Vassalli, P. & Stamenkovic, I. Redirection of tumor metastasis by expression of E-selectin in vivo. J. Exp. Med. 183, 581–587 (1996).

    CAS  PubMed  Google Scholar 

  100. 100

    Mannori, G. et al. Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin. Am. J. Pathol. 151, 233–243 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101

    Napier, S. L., Healy, Z. R., Schnaar, R. L. & Konstantopoulos, K. Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44V and alternative sialofucosylated selectin ligands. J. Biol. Chem. 282, 3433–3441 (2007).

    CAS  PubMed  Google Scholar 

  102. 102

    Thomas, S. N., Schnaar, R. L. & Konstantopoulos, K. Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells. Am. J. Physiol. Cell Physiol. 296, C505–C513 (2009).

    CAS  PubMed  Google Scholar 

  103. 103

    Thomas, S. N., Zhu, F., Schnaar, R. L., Alves, C. S. & Konstantopoulos, K. Carcinoembryonic antigen and CD44v cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J. Biol. Chem. 283, 15647–15655 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104

    Konstantopoulos, K. & Thomas, S. N. Cancer cells in transit: the vascular interactions of tumor cells. Annu. Rev. Biomed. Eng. 11, 177–202 (2009).

    CAS  PubMed  Google Scholar 

  105. 105

    Varki, A., Varki, N. M. & Borsig, L. Molecular basis of metastasis. N. Engl. J. Med. 360, 1678–1679; author reply 1679–1680 (2009).

    CAS  PubMed  Google Scholar 

  106. 106

    Jain, S. et al. Platelet glycoprotein Ibα supports experimental lung metastasis. Proc. Natl Acad. Sci. USA 104, 9024–9028 (2007).

    CAS  PubMed  Google Scholar 

  107. 107

    Jain, S., Russell, S. & Ware, J. Platelet glycoprotein VI facilitates experimental lung metastasis in syngenic mouse models. J. Thromb. Haemost. 7, 1713–1717 (2009).

    CAS  PubMed  Google Scholar 

  108. 108

    Weiss, L. Patterns of metastasis. Cancer Metastasis Rev. 19, 281–301 (2000).

    Google Scholar 

  109. 109

    Jacob, K., Sollier, C. & Jabado, N. Circulating tumor cells: detection, molecular profiling and future prospects. Expert Rev. Proteomics 4, 741–756 (2007).

    CAS  PubMed  Google Scholar 

  110. 110

    Fidler, I. J. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature Rev. Cancer 3, 453–458 (2003).

    CAS  Google Scholar 

  111. 111

    Weiss, L. Comments on hematogenous metastatic patterns in humans as revealed by autopsy. Clin. Exp. Metastasis 10, 191–199 (1992).

    CAS  PubMed  Google Scholar 

  112. 112

    Paget, S. The distribution of secondary growths in cancer of the breast. Lancet 1, 571–573 (1889).

    Google Scholar 

  113. 113

    Trepel, M., Arap, W. & Pasqualini, R. In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr. Opin. Chem. Biol. 6, 399–404 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114

    Chang, S. F. et al. Tumor cell cycle arrest induced by shear stress: roles of integrins and Smad. Proc. Natl Acad. Sci. USA 105, 3927–3932 (2008).

    CAS  PubMed  Google Scholar 

  115. 115

    Lawler, K., O'Sullivan, G., Long, A. & Kenny, D. Shear stress induces internalization of E-cadherin and invasiveness in metastatic oesophageal cancer cells by a Src-dependent pathway. Cancer Sci. 100, 1082–1087 (2009).

    CAS  PubMed  Google Scholar 

  116. 116

    Raub, C. B. et al. Noninvasive assessment of collagen gel microstructure and mechanics using multiphoton microscopy. Biophys. J. 92, 2212–2222 (2007).

    CAS  PubMed  Google Scholar 

  117. 117

    Griffith, L. G. & Swartz, M. A. Capturing complex 3D tissue physiology in vitro. Nature Rev. Mol. Cell Biol. 7, 211–224 (2006).

    CAS  Google Scholar 

  118. 118

    Buxboim, A., Ivanovska, I. L. & Discher, D. E. Matrix elasticity, cytoskeletal forces and physics of the nucleus: how deeply do cells 'feel' outside and in? J. Cell Sci. 123, 297–308 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Goldman, A. J., Cox, R. G. & Brenner, H. Slow viscous motion of a sphere parallel to a plane wall — 2 Couette flow. Chem. Eng. Sci. 22, 653–660 (1967).

    CAS  Google Scholar 

  120. 120

    Hanley, W. D., Wirtz, D. & Konstantopoulos, K. Distinct kinetic and mechanical properties govern selectin-leukocyte interactions. J. Cell Sci. 117, 2503–2511 (2004).

    CAS  PubMed  Google Scholar 

  121. 121

    Panorchan, P. et al. Single-molecule analysis of cadherin-mediated cell-cell adhesion. J. Cell Sci. 119, 66–74 (2006).

    CAS  PubMed  Google Scholar 

  122. 122

    Raman, P., Alves, C., Wirtz, D. & Konstantopoulos, K. Single molecule binding of CD44 to fibrin versus P-selectin predicts their distinct shear-dependent interactions in cancer. J. Cell Sci. 124, 1903–1910 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Li, F., Redick, S. D., Erickson, H. P. & Moy, V. T. Force measurements of the α5β1 integrin-fibronectin interaction. Biophys. J. 84, 1252–1262 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124

    Bajpai, S. et al. α-Catenin mediates initial E-cadherin-dependent cell-cell recognition and subsequent bond strengthening. Proc. Natl Acad. Sci. USA 105, 18331–18336 (2008).

    CAS  PubMed  Google Scholar 

  125. 125

    Bajpai, S., Feng, Y., Krishnamurthy, R., Longmore, G. D. & Wirtz, D. Loss of α-catenin decreases the strength of single E-cadherin bonds between human cancer cells. J. Biol. Chem. 284, 18252–18259 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. 126

    Garcia, A. J., Ducheyne, P. & Boettiger, D. Quantification of cell adhesion using a spinning disc device and application to surface-reactive materials. Biomaterials 18, 1091–1098 (1997).

    CAS  PubMed  Google Scholar 

  127. 127

    DeGrendele, H. C., Kosfiszer, M., Estess, P. & Siegelman, M. H. CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation. J. Immunol. 159, 2549–2553 (1997).

    CAS  Google Scholar 

  128. 128

    Palecek, S. P., Loftus, J. C., Ginsberg, M. H., Lauffenburger, D. A. & Horwitz, A. F. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537–540 (1997).

    CAS  PubMed  Google Scholar 

  129. 129

    Azioune, A., Storch, M., Bornens, M., Thery, M. & Piel, M. Simple and rapid process for single cell micro-patterning. Lab. Chip 9, 1640–1642 (2009).

    CAS  PubMed  Google Scholar 

  130. 130

    Thery, M. & Bornens, M. Cell shape and cell division. Curr. Opin. Cell Biol. 18, 648–657 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

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

    CAS  PubMed  Google Scholar 

  132. 132

    Chen, C. S., Mrksich, M., Huang, S., Whitesides, G. M. & Ingber, D. E. Geometric control of cell life and death. Science 276, 1425–1428 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133

    Mali, P., Wirtz, D. & Searson, P. C. Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis. Biophys. J. 99, 3526–3534 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. 134

    Wildt, B., Wirtz, D. & Searson, P. C. Programmed subcellular release for studying the dynamics of cell detachment. Nature Methods 6, 211–213 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. 135

    Wildt, B., Wirtz, D. & Searson, P. C. Triggering cell detachment from patterned electrode arrays by programmed subcellular release. Nature Protoc. 5, 1273–1280 (2010).

    CAS  Google Scholar 

  136. 136

    Ghaly, T., Wildt, B. E. & Searson, P. C. Electrochemical release of fluorescently labeled thiols from patterned gold surfaces. Langmuir 26, 1420–1423 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137

    Sniadecki, N. J., Lamb, C. M., Liu, Y., Chen, C. S. & Reich, D. H. Magnetic microposts for mechanical stimulation of biological cells: fabrication, characterization, and analysis. Rev. Sci. Instrum. 79, 044302 (2008).

    PubMed  PubMed Central  Google Scholar 

  138. 138

    Tan, J. L. et al. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl Acad. Sci. USA 100, 1484–1489 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. 139

    Dembo, M. & Wang, Y. L. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys. J. 76, 2307–2316 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 140

    Song, B. et al. Application of direct current electric fields to cells and tissues in vitro and modulation of wound electric field in vivo. Nature Protoc. 2, 1479–1489 (2007).

    CAS  Google Scholar 

  141. 141

    Huang, C. W., Cheng, J. Y., Yen, M. H. & Young, T. H. Electrotaxis of lung cancer cells in a multiple-electric-field chip. Biosens. Bioelectron. 24, 3510–3516 (2009).

    CAS  PubMed  Google Scholar 

  142. 142

    Lee, J. S., Chang, M. I., Tseng, Y. & Wirtz, D. Cdc42 mediates nucleus movement and MTOC polarization in Swiss 3T3 fibroblasts under mechanical shear stress. Mol. Biol. Cell 16, 871–880 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 143

    Wojciak-Stothard, B. & Ridley, A. J. Shear stress-induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases. J. Cell Biol. 161, 429–439 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144

    Gomes, E. R., Jani, S. & Gundersen, G. G. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121, 451–463 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. 145

    Poujade, M. et al. Collective migration of an epithelial monolayer in response to a model wound. Proc. Natl Acad. Sci. USA 104, 15988–15993 (2007).

    CAS  Google Scholar 

  146. 146

    Daniels, B. R., Masi, B. C. & Wirtz, D. Probing single-cell micromechanics in vivo: the microrheology of C. elegans developing embryos. Biophys. J. 90, 4712–4719 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. 147

    Massiera, G., Van Citters, K. M., Biancaniello, P. L. & Crocker, J. C. Mechanics of single cells: rheology, time dependence, and fluctuations. Biophys. J. 93, 3703–3713 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. 148

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

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149

    Zhou, X. et al. Fibronectin fibrillogenesis regulates three-dimensional neovessel formation. Genes Dev. 22, 1231–1243 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150

    Wang, N., Butler, J. P. & Ingber, D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124–1127 (1993).

    CAS  Google Scholar 

  151. 151

    Rahman, A., Tseng, Y. & Wirtz, D. Micromechanical coupling between cell surface receptors and RGD peptides. Biochem. Biophys. Res. Commun. 296, 771–778 (2002).

    CAS  PubMed  Google Scholar 

  152. 152

    Kishino, A. & Yanagida, T. Force measurements by micromanipulation of a single actin filament by glass needles. Nature 334, 74–76 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. 153

    Zheng, J. et al. Tensile regulation of axonal elongation and initiation. J. Neurosci. 11, 1117–1125 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154

    Kumar, S. et al. Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics. Biophys. J. 90, 3762–3773 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. 155

    Grill, S. W., Gonczy, P., Stelzer, E. H. & Hyman, A. A. Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo. Nature 409, 630–633 (2001).

    CAS  Google Scholar 

  156. 156

    Grill, S. W., Howard, J., Schaffer, E., Stelzer, E. H. & Hyman, A. A. The distribution of active force generators controls mitotic spindle position. Science 301, 518–521 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Pajerowski, J. D., Dahl, K. N., Zhong, F. L., Sammak, P. J. & Discher, D. E. Physical plasticity of the nucleus in stem cell differentiation. Proc. Natl Acad. Sci. USA 104, 15619–15624 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. 158

    Hochmuth, R. M. Micropipette aspiration of living cells. J. Biomech. 33, 15–22 (2000).

    CAS  PubMed  Google Scholar 

  159. 159

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. 160

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

    CAS  Google Scholar 

  161. 161

    Gerecht, S. et al. The effect of actin disrupting agents on contact guidance of human embryonic stem cells. Biomaterials 28, 4068–4077 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. 162

    Karuri, N. W. et al. Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells. J. Cell Sci. 117, 3153–3164 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. 163

    Teixeira, A. I., Abrams, G. A., Bertics, P. J., Murphy, C. J. & Nealey, P. F. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J. Cell Sci. 116, 1881–1892 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. 164

    Kaspar, D., Seidl, W., Neidlinger-Wilke, C., Ignatius, A. & Claes, L. Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity. J. Biomech. 33, 45–51 (2000).

    CAS  PubMed  Google Scholar 

  165. 165

    Hubbell, J. Biomaterials in tissue engineering. Biotechnology 13, 565–576 (1995).

    CAS  PubMed  Google Scholar 

  166. 166

    Irimia, D. & Toner, M. Spontaneous migration of cancer cells under conditions of mechanical confinement. Integr Biol. (Camb.) 1, 506–512 (2009).

    CAS  Google Scholar 

  167. 167

    Wang, C. J. & Levchenko, A. Microfluidics technology for systems biology research. Methods Mol. Biol. 500, 203–219 (2009).

    CAS  PubMed  Google Scholar 

  168. 168

    Sundararaghavan, H. G., Monteiro, G. A., Firestein, B. L. & Shreiber, D. I. Neurite growth in 3D collagen gels with gradients of mechanical properties. Biotechnol. Bioeng. 102, 632–643 (2009).

    CAS  PubMed  Google Scholar 

  169. 169

    Quake, S. R. & Scherer, A. From micro- to nanofabrication with soft materials. Science 290, 1536–1540 (2000).

    CAS  PubMed  Google Scholar 

  170. 170

    Rogers, S. S., Waigh, T. A. & Lu, J. R. Intracellular microrheology of motile Amoeba proteus. Biophys. J. 94, 3313–3322 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. 171

    Condeelis, J. & Segall, J. E. Intravital imaging of cell movement in tumours. Nature Rev. Cancer 3, 921–930 (2003).

    CAS  Google Scholar 

  172. 172

    Kedrin, D. et al. Intravital imaging of metastatic behavior through a mammary imaging window. Nature Methods 5, 1019–1021 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. 173

    Phair, R. D. & Misteli, T. High mobility of proteins in the mammalian cell nucleus. Nature 404, 604–609 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. 174

    Phair, R. D. & Misteli, T. Kinetic modelling approaches to in vivo imaging. Nature Rev. Mol. Cell Biol. 2, 898–907 (2001).

    CAS  Google Scholar 

  175. 175

    Pertz, O. & Hahn, K. M. Designing biosensors for Rho family proteins — deciphering the dynamics of Rho family GTPase activation in living cells. J. Cell Sci. 117, 1313–1318 (2004).

    CAS  PubMed  Google Scholar 

  176. 176

    Nalbant, P., Hodgson, L., Kraynov, V., Toutchkine, A. & Hahn, K. M. Activation of endogenous Cdc42 visualized in living cells. Science 305, 1615–1619 (2004).

    CAS  PubMed  Google Scholar 

  177. 177

    Moerner, W. E. & Orrit, M. Illuminating single molecules in condensed matter. Science 283, 1670–1676 (1999).

    CAS  PubMed  Google Scholar 

  178. 178

    Magde, D., Elson, E. L. & Webb, W. W. Fluorescence correlation spectroscopy. II. An experimental realization. Biopolymers 13, 29–61 (1974).

    CAS  PubMed  Google Scholar 

  179. 179

    Daniels, B. R., Perkins, E. M., Dobrowsky, T. M., Sun, S. X. & Wirtz, D. Asymmetric enrichment of PIE-1 in the Caenorhabditis elegans zygote mediated by binary counterdiffusion. J. Cell Biol. 184, 473–479 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. 180

    Huang, B., Bates, M. & Zhuang, X. Super-resolution fluorescence microscopy. Annu. Rev. Biochem. 78, 993–1016 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  181. 181

    Huang, B., Wang, W., Bates, M. & Zhuang, X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science 319, 810–813 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. 182

    Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642–1645 (2006).

    CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge support from the US National Institutes of Health (grants U54CA143868, U54CA151838 and RO1CA101135).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Denis Wirtz or Konstantinos Konstantopoulos or Peter C. Searson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Glossary

Amoeboid migration

A mode of three-dimensional cell migration in a matrix that involves dynamic cell-shape changes through actomyosin assembly and contractility, and adhesion to the extracellular matrix.

Epithelial-to-mesenchymal transition

(EMT). A morphological change that epithelial cells undergo, from a cubical to an elongated shape, following oncogenic transformation, which is often accompanied by loss of expression of the adhesion molecule E-cadherin. Post-EMT, cells adopt a high-motility phenotype.

Filopodia

Narrow projections of the cytoplasm extended beyond the lamellipodia of migrating cells. Filopodia are associated with the formation of nascent focal adhesions with a substratum.

Focal adhesions

Integrin clusters located at the basal surface of adherent cells that connect the extracellular matrix to the cytoskeleton through focal adhesion proteins.

Interstitial flow

Fluid flow in the extracellular matrix, often associated with lymphatic drainage of plasma back to the vascular system.

Intravital microscopy

A microscopy technique used for the observation of biological responses, such as leukocyteendothelial cell interactions, in living tissues in real time. Translucent tissues are commonly used, such as the mesentery or cremaster muscle, which can be easily exteriorized for microscopic observation.

Lamellipodia

Large cytoplasmic projects found primarily at the leading edge of migrating cells, particularly on two-dimensional substrates.

Mechanosensing

The ability of cells to sense and respond to changes in the mechanical compliance of a substrate. Mechanosensing is mediated by focal adhesions and the cytoskeleton in two-dimensional cell culture.

Mesenchymal migration

A mode of three-dimensional cell migration in a matrix that involves integrin-based adhesion. Mesenchymal migration occurs when the pore size of the matrix is much smaller than the cell nucleus.

Pseudopodia

Bulges of constantly changing shape observed in the plasma membrane of migrating cells during amoeboid migration on two-dimensional substrates and mesenchymal migration through three-dimensional matrices.

Shear rate

The relative velocities of adjacent layers of fluid under shear force in conditions of laminar flow.

Shear stress

The magnitude of the tangential force applied onto the surface of an object per unit area. Shear stress is expressed in units of force per unit area (Newtons m−2 in metres kilograms seconds (MKS) units or dynes cm−2 in centimetres grams seconds (CGS) units).

Stiffness

(Also known as elasticity or elastic modulus). A measure of the ability of a material to resist shear forces similarly to a solid. Rubber is elastic and shows little viscosity. A crosslinked collagen matrix is elastic, but not viscous as it does not flow. The cytoplasm of cells is both elastic and viscous (viscoelastic) depending on the rate of deformation.

Stress fibres

Contractile actin filament bundles that contain myosin II, which serves both as an F-actin bundling protein and as a force generator. Stress fibres terminate at focal adhesions at the basal surface of cells on substrates.

Surface tangential velocity

The velocity at the surface of a spinning object.

Translational velocity

The velocity of an object in space.

Viscosity

A measure of the ability of a material to flow like a liquid. Water, glycerol and honey are liquids of increasing viscosity; they are only viscous and show no elasticity.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wirtz, D., Konstantopoulos, K. & Searson, P. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 11, 512–522 (2011). https://doi.org/10.1038/nrc3080

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing