CoChat
Sign Up
Cited by 908Cellular Mechanics and InteractionsCell Adhesion Molecules ResearchForce Microscopy Techniques and Applications

The relationship between force and focal complex development

Open access
Galbraith, Catherine G., Yamada, Kenneth M., Sheetz, Michael P.·2002·The Journal of Cell Biology
DOI 10.1083/jcb.200204153PMC PMC2173098
Open this paper in CoChat — free accountOpen PDF

Abstract

To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin–ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin–ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1083/jcb.200204153

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Earlier in vitro work indicated vinculin as a crucial effector of cadherin-mediated mechanotransduction.

    “Earlier in vitro work indicated vinculin as a crucial effector of cadherin-mediated mechanotransduction38–42.”

    From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [41]

    The Discussion (page unavailable) suggests vinculin has an essential role in strengthening force-dependent adhesions, but specifies connections between integrin receptors and the cytoskeleton. It does not establish vinculin as a crucial effector of cadherin-mediated mechanotransduction. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 41

  1. Balaban, N.Q., U.S. Schwarz, D. Riveline, P. Goichberg, G. Tzur, I. Sabanay, D. Mahalu, S. Safran, A. Bershadsky, L. Addadi, and B. Geiger. 2001. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3: 466–472. 11331874
  2. Beningo, K.A., M. Dembo, I. Kaverina, J.V. Small, and Y.L. Wang. 2001. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153: 881–888. 11352946 PMC2192381
  3. Bloom, L., K.C. Ingham, and R.O. Hynes. 1999. Fibronectin regulates assembly of actin filaments and focal contacts in cultured cells via the heparin-binding site in repeat III13. Mol. Biol. Cell. 10: 1521–1536. 10233160 PMC25325
  4. Chen, C.S., M. Mrksich, S. Huang, G.M. Whitesides, and D.E. Ingber. 1997. Geometric control of cell life and death. Science. 276: 1425–1428. 9162012
  5. Choquet, D., D.P. Felsenfeld, and M.P. Sheetz. 1997. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell. 88: 39–48. 9019403
  6. Coso, O.A., M. Chiariello, J.C. Yu, H. Teramoto, P. Crespo, N. Xu, T. Miki, and J.S. Gutkind. 1995. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 81: 1137–1146. 7600581
  7. DePasquale, J.A., and C.S. Izzard. 1987. 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. 105: 2803–2809. 3121637 PMC2114683
  8. Evans, E. 1993. New physical concepts for cell amoeboid motion. Biophys. J. 64: 1306–1322. 8494986 PMC1262449
  9. Felsenfeld, D.P., P.L. Schwartzberg, A. Venegas, R. Tse, and M.P. Sheetz. 1999. Selective regulation of integrin–cytoskeleton interactions by the tyrosine kinase Src. Nat. Cell Biol. 1: 200–206. 10559917
  10. Galbraith, C.G., and M.P. Sheetz. 1997. A micromachined device provides a new bend on fibroblast traction forces. Proc. Natl. Acad. Sci. USA. 94: 9114–9118. 9256444 PMC23061
  11. Galbraith, C.G., and M.P. Sheetz. 1999. Keratocytes pull with similar forces on their dorsal and ventral surfaces. J. Cell Biol. 147: 1313–1324. 10601343 PMC2168090
  12. Galbraith, C.G., R. Skalak, and S. Chien. 1998. Shear stress induces spatial reorganization of the endothelial cell cytoskeleton. Cell Motil. Cytoskeleton. 40: 317–330. 9712262
  13. Geiger, B., and A. Bershadsky. 2001. Assembly and mechanosensory function of focal contacts. Curr. Opin. Cell Biol. 13: 584–592. 11544027
  14. Geiger, B., A. Bershadsky, R. Pankov, and K.M. Yamada. 2001. Transmembrane crosstalk between the extracellular matrix and the cytoskeleton. Nat. Rev. Mol. Cell Biol. 2: 793–805. 11715046
  15. Grinnell, F., and B. Geiger. 1986. Interaction of fibronectin-coated beads with attached and spread fibroblasts. Binding, phagocytosis, and cytoskeletal reorganization. Exp. Cell Res. 162: 449–461. 3080317
  16. Izzard, C.S. 1988. A precursor of the focal contact in cultured fibroblasts. Cell Motil. Cytoskeleton. 10: 137–142. 3141068
  17. Izzard, C.S., R. Radinsky, and L.A. Culp. 1986. Substratum contacts and cytoskeletal reorganization of BALB/c 3T3 cells on a cell-binding fragment and heparin-binding fragments of plasma fibronectin. Exp. Cell Res. 165: 320–336. 3720853
  18. Kraynov, V.S., C. Chamberlain, G.M. Bokoch, M.A. Schwartz, S. Slabaugh, and K.M. Hahn. 2000. Localized Rac activation dynamics visualized in living cells. Science. 290: 333–337. 11030651
  19. Lauffenburger, D.A., and A.F. Horwitz. 1996. Cell migration: a physically integrated molecular process. Cell. 84: 359–369. 8608589
  20. Lee, J., M. Leonard, T. Oliver, A. Ishihara, and K. Jacobson. 1994. Traction forces generated by locomoting keratocytes. J. Cell Biol. 127: 1957–1964. 7806573 PMC2120302
  21. Lo, C.M., H.B. Wang, M. Dembo, and Y.L. Wang. 2000. Cell movement is guided by the rigidity of the substrate. Biophys. J. 79: 144–152. 10866943 PMC1300921
  22. Mandeville, J.T., M.A. Lawson, and F.R. Maxfield. 1997. Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix. J. Leukoc. Biol. 61: 188–200. 9021925
  23. Miyamoto, S., S.K. Akiyama, and K.M. Yamada. 1995. Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science. 267: 883–885. 7846531
  24. Nobes, C.D., and A. Hall. 1995. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 81: 53–62. 7536630
  25. Palecek, S.P., J.C. Loftus, M.H. Ginsberg, D.A. Lauffenburger, and A.F. Horwitz. 1997. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature. 385: 537–540. 9020360
  26. Pelham, R.J., and Y. Wang. 1999. High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. Mol. Biol. Cell. 10: 935–945. 10198048 PMC25217
  27. Regen, C.M., and A.F. Horwitz. 1992. Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts. J. Cell Biol. 119: 1347–1359. 1280274 PMC2289731
  28. Riveline, D., E. Zamir, N.Q. Balaban, U.S. Schwarz, T. Ishizaki, S. Narumiya, Z. Kam, B. Geiger, and A.D. Bershadsky. 2001. 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: 1175–1186. 11402062 PMC2192034
  29. Rottner, K., A. Hall, and J.V. Small. 1999. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9: 640–648. 10375527
  30. Saoncella, S., F. Echtermeyer, F. Denhez, J.K. Nowlen, D.F. Mosher, S.D. Robinson, R.O. Hynes, and P.F. Goetinck. 1999. Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers. Proc. Natl. Acad. Sci. USA. 96: 2805–2810. 10077592 PMC15850
  31. Sastry, S.K., and K. Burridge. 2000. Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp. Cell Res. 261: 25–36. 11082272
  32. Sheetz, M.P., D.P. Felsenfeld, and C.G. Galbraith. 1998. Cell migration: regulation of force on extracellular-matrix-integrin complexes. Trends Cell Biol. 8: 51–54. 9695809
  33. Sterba, R.E., and M.P. Sheetz. 1998. Basic laser tweezers. Methods Cell Biol. 55: 29–41. 9352509
  34. Suzuki, K., R.E. Sterba, and M.P. Sheetz. 2000. Outer membrane monolayer domains from two-dimensional surface scanning resistance measurements. Biophys. J. 79: 448–459. 10866970 PMC1300948
  35. Svitkina, T.M., A.B. Verkhovsky, K.M. McQuade, and G.G. Borisy. 1997. Analysis of the actin-myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J. Cell Biol. 139: 397–415. 9334344 PMC2139803
  36. Svoboda, K., and S.M. Block. 1994. Biological applications of optical forces. Annu. Rev. Biophys. Biomol. Struct. 23: 247–285. 7919782
  37. Volberg, T., B. Geiger, Z. Kam, R. Pankov, I. Simcha, H. Sabanay, J.L. Coll, E. Adamson, and A. Ben-Ze'ev. 1995. Focal adhesion formation by F9 embryonal carcinoma cells after vinculin gene disruption. J. Cell Sci. 108: 2253–2260. 7673345
  38. Vuori, K., and E. Ruoslahti. 1999. Connections count in cell migration. Nat. Cell Biol. 1: E85–E87. 10559926
  39. Woods, A., J.R. Couchman, S. Johansson, and M. Hook. 1986. Adhesion and cytoskeletal organisation of fibroblasts in response to fibronectin fragments. EMBO J. 5: 665–670. 3709521 PMC1166842
  40. Xu, W., H. Baribault, and E.D. Adamson. 1998. Vinculin knockout results in heart and brain defects during embryonic development. Development. 125: 327–337. 9486805
  41. Zamir, E., M. Katz, Y. Posen, N. Erez, K.M. Yamada, B.Z. Katz, S. Lin, D.C. Lin, A. Bershadsky, Z. Kam, and B. Geiger. 2000. Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat. Cell Biol. 2: 191–196. 10783236

Cited by

Sorted by citations

Authors
Galbraith, C. G., Yamada, K. M., & Sheetz, M. P.
Affiliations
  • National Institutes of Health (US)
  • Duke University (US)
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2002-11-25
Volume
159
Issue
4
Pages
695-705
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200204153
PMC
PMC2173098
OpenAlex
W2068092779
Cited by
908
References
0
Citations by year
2026: 9 · 2025: 15 · 2024: 6 · 2023: 23 · 2022: 22 · 2021: 27 · 2020: 32 · 2019: 32 · 2018: 26 · 2017: 36 · 2016: 48 · 2015: 44 · 2014: 68 · 2013: 58 · 2012: 66
FWCI
10.67
Type
journal article
Language
en
Open access
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Office of Naval Research (N00014)
  • National Institute of General Medical Sciences (R01GM036277, GM 36277-15)
  • National Institute of Dental and Craniofacial Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
Keywords
vinculin, focal adhesions, cytoskeletal forces, alpha5beta1 integrin, integrin αvβ3, Src kinase, lamellipodia
MeSH terms
CSK Tyrosine-Protein Kinase, Animals, Cell Adhesion, Cell Movement, Concanavalin A, Cytoskeleton, Extracellular Matrix, Fibronectins, Ligands, Models, Biological, Protein-Tyrosine Kinases, Recombinant Fusion Proteins, Integrins, 3T3 Cells, Vinculin, src-Family Kinases, Vitronectin, Focal Adhesions, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review