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Biophys J. Jul 2000; 79(1): 144–152.
PMCID: PMC1300921

Cell movement is guided by the rigidity of the substrate.

Abstract

Directional cell locomotion is critical in many physiological processes, including morphogenesis, the immune response, and wound healing. It is well known that in these processes cell movements can be guided by gradients of various chemical signals. In this study, we demonstrate that cell movement can also be guided by purely physical interactions at the cell-substrate interface. We cultured National Institutes of Health 3T3 fibroblasts on flexible polyacrylamide sheets coated with type I collagen. A transition in rigidity was introduced in the central region of the sheet by a discontinuity in the concentration of the bis-acrylamide cross-linker. Cells approaching the transition region from the soft side could easily migrate across the boundary, with a concurrent increase in spreading area and traction forces. In contrast, cells migrating from the stiff side turned around or retracted as they reached the boundary. We call this apparent preference for a stiff substrate "durotaxis." In addition to substrate rigidity, we discovered that cell movement could also be guided by manipulating the flexible substrate to produce mechanical strains in the front or rear of a polarized cell. We conclude that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion.

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Selected References

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  • Bernstein LR, Liotta LA. Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis. Curr Opin Oncol. 1994 Jan;6(1):106–113. [PubMed]
  • Bray D. Axonal growth in response to experimentally applied mechanical tension. Dev Biol. 1984 Apr;102(2):379–389. [PubMed]
  • Brown MJ, Loew LM. Electric field-directed fibroblast locomotion involves cell surface molecular reorganization and is calcium independent. J Cell Biol. 1994 Oct;127(1):117–128. [PMC free article] [PubMed]
  • Carter SB. Principles of cell motility: the direction of cell movement and cancer invasion. Nature. 1965 Dec 18;208(5016):1183–1187. [PubMed]
  • Carter SB. Haptotaxis and the mechanism of cell motility. Nature. 1967 Jan 21;213(5073):256–260. [PubMed]
  • Chada S, Lamoureux P, Buxbaum RE, Heidemann SR. Cytomechanics of neurite outgrowth from chick brain neurons. J Cell Sci. 1997 May;110(Pt 10):1179–1186. [PubMed]
  • Choquet D, Felsenfeld DP, Sheetz MP. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell. 1997 Jan 10;88(1):39–48. [PubMed]
  • Curtis A, Wilkinson C. Topographical control of cells. Biomaterials. 1997 Dec;18(24):1573–1583. [PubMed]
  • Curtis A, Wilkinson C. New depths in cell behaviour: reactions of cells to nanotopography. Biochem Soc Symp. 1999;65:15–26. [PubMed]
  • Dembo M, Wang YL. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys J. 1999 Apr;76(4):2307–2316. [PMC free article] [PubMed]
  • DePasquale JA, Izzard CS. Evidence for an actin-containing cytoplasmic precursor of the focal contact and the timing of incorporation of vinculin at the focal contact. J Cell Biol. 1987 Dec;105(6 Pt 1):2803–2809. [PMC free article] [PubMed]
  • Dunn GA, Brown AF. Alignment of fibroblasts on grooved surfaces described by a simple geometric transformation. J Cell Sci. 1986 Jul;83:313–340. [PubMed]
  • Erickson CA, Nuccitelli R. Embryonic fibroblast motility and orientation can be influenced by physiological electric fields. J Cell Biol. 1984 Jan;98(1):296–307. [PMC free article] [PubMed]
  • Halliday NL, Tomasek JJ. Mechanical properties of the extracellular matrix influence fibronectin fibril assembly in vitro. Exp Cell Res. 1995 Mar;217(1):109–117. [PubMed]
  • Harris A. Behavior of cultured cells on substrata of variable adhesiveness. Exp Cell Res. 1973 Mar 15;77(1):285–297. [PubMed]
  • Harris AK, Stopak D, Wild P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature. 1981 Mar 19;290(5803):249–251. [PubMed]
  • Huttenlocher A, Ginsberg MH, Horwitz AF. Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. J Cell Biol. 1996 Sep;134(6):1551–1562. [PMC free article] [PubMed]
  • Juliano RL, Haskill S. Signal transduction from the extracellular matrix. J Cell Biol. 1993 Feb;120(3):577–585. [PMC free article] [PubMed]
  • Keely PJ, Fong AM, Zutter MM, Santoro SA. Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells. J Cell Sci. 1995 Feb;108(Pt 2):595–607. [PubMed]
  • Kolega J. Effects of mechanical tension on protrusive activity and microfilament and intermediate filament organization in an epidermal epithelium moving in culture. J Cell Biol. 1986 Apr;102(4):1400–1411. [PMC free article] [PubMed]
  • Lamoureux P, Buxbaum RE, Heidemann SR. Direct evidence that growth cones pull. Nature. 1989 Jul 13;340(6229):159–162. [PubMed]
  • Lauffenburger DA, Horwitz AF. Cell migration: a physically integrated molecular process. Cell. 1996 Feb 9;84(3):359–369. [PubMed]
  • Lee J, Ishihara A, Oxford G, Johnson B, Jacobson K. Regulation of cell movement is mediated by stretch-activated calcium channels. Nature. 1999 Jul 22;400(6742):382–386. [PubMed]
  • Lowe B. The role of Ca2+ in deflection-induced excitation of motile, mechanoresponsive balancer cilia in the ctenophore statocyst. J Exp Biol. 1997 Jun;200(Pt 11):1593–1606. [PubMed]
  • Mandeville JT, Lawson MA, Maxfield FR. Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix. J Leukoc Biol. 1997 Feb;61(2):188–200. [PubMed]
  • Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997 Apr 4;276(5309):75–81. [PubMed]
  • Oakley C, Jaeger NA, Brunette DM. Sensitivity of fibroblasts and their cytoskeletons to substratum topographies: topographic guidance and topographic compensation by micromachined grooves of different dimensions. Exp Cell Res. 1997 Aug 1;234(2):413–424. [PubMed]
  • Pelham RJ, Jr, Wang Y l. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661–13665. [PMC free article] [PubMed]
  • Pelham RJ, Jr, Wang Y l. High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. Mol Biol Cell. 1999 Apr;10(4):935–945. [PMC free article] [PubMed]
  • Pettit EJ, Fay FS. Cytosolic free calcium and the cytoskeleton in the control of leukocyte chemotaxis. Physiol Rev. 1998 Oct;78(4):949–967. [PubMed]
  • Radmacher M, Tillamnn RW, Fritz M, Gaub HE. From molecules to cells: imaging soft samples with the atomic force microscope. Science. 1992 Sep 25;257(5078):1900–1905. [PubMed]
  • Saranak J, Foster KW. Rhodopsin guides fungal phototaxis. Nature. 1997 May 29;387(6632):465–466. [PubMed]
  • Schwarzbauer JE, Sechler JL. Fibronectin fibrillogenesis: a paradigm for extracellular matrix assembly. Curr Opin Cell Biol. 1999 Oct;11(5):622–627. [PubMed]
  • Sheetz MP, Felsenfeld DP, Galbraith CG. Cell migration: regulation of force on extracellular-matrix-integrin complexes. Trends Cell Biol. 1998 Feb;8(2):51–54. [PubMed]
  • Toyoizumi R, Takeuchi S. The behavior of chick gastrula mesodermal cells under the unidirectional tractive force parallel to the substrata. J Cell Sci. 1995 Feb;108(Pt 2):557–567. [PubMed]
  • Tranquillo RT. Self-organization of tissue-equivalents: the nature and role of contact guidance. Biochem Soc Symp. 1999;65:27–42. [PubMed]
  • Verkhovsky AB, Svitkina TM, Borisy GG. Self-polarization and directional motility of cytoplasm. Curr Biol. 1999 Jan 14;9(1):11–20. [PubMed]
  • Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993 May 21;260(5111):1124–1127. [PubMed]
  • Wang YL, Pelham RJ., Jr Preparation of a flexible, porous polyacrylamide substrate for mechanical studies of cultured cells. Methods Enzymol. 1998;298:489–496. [PubMed]

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