Environmental Sensing Through Focal Adhesions

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2009 Feb 7

PMID 19197329

Citations 964

Authors

Benjamin Geiger

Joachim P Spatz

Alexander D Bershadsky

Affiliations

Soon will be listed here.

Abstract

Recent progress in the design and application of artificial cellular microenvironments and nanoenvironments has revealed the extraordinary ability of cells to adjust their cytoskeletal organization, and hence their shape and motility, to minute changes in their immediate surroundings. Integrin-based adhesion complexes, which are tightly associated with the actin cytoskeleton, comprise the cellular machinery that recognizes not only the biochemical diversity of the extracellular neighbourhood, but also its physical and topographical characteristics, such as pliability, dimensionality and ligand spacing. Here, we discuss the mechanisms of such environmental sensing, based on the finely tuned crosstalk between the assembly of one type of integrin-based adhesion complex, namely focal adhesions, and the forces that are at work in the associated cytoskeletal network owing to actin polymerization and actomyosin contraction.

Citing Articles

Spheroids from Epithelial and Mesenchymal Cell Phenotypes as Building Blocks in Bioprinting (Review).

Revokatova D, Koteneva P, Kosheleva N, Shpichka A, Timashev P Sovrem Tekhnologii Med. 2025; 17(1):133-154.

PMID: 40071071 PMC: 11892564. DOI: 10.17691/stm2025.17.1.11.

Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.

Liu Z, Zhang X, Ben T, Li M, Jin Y, Wang T Biomark Res. 2025; 13(1):38.

PMID: 40045379 PMC: 11884212. DOI: 10.1186/s40364-025-00745-7.

Effects of hydrogel stiffness and viscoelasticity on organoid culture: a comprehensive review.

Lai W, Geliang H, Bin X, Wang W Mol Med. 2025; 31(1):83.

PMID: 40033190 PMC: 11877758. DOI: 10.1186/s10020-025-01131-7.

Focal Adhesion Kinase Alleviates Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation by Activating Transcriptional Wnt/β-Catenin-BMP2-COL1 and Metabolic SIRT1-PGC-1α-CPT1A Pathways.

Bai Y, Wu Z, Leary S, Fang C, Yu M, Genth H Int J Mol Sci. 2025; 26(4).

PMID: 40004131 PMC: 11855299. DOI: 10.3390/ijms26041669.

Transcriptomic Analysis Divulges Differential Expressions of Microglial Genes After Microglial Repopulation in Mice.

Hafeez M, Gao H, Ju F, Qi F, Li T, Zhang S Int J Mol Sci. 2025; 26(4).

PMID: 40003960 PMC: 11855859. DOI: 10.3390/ijms26041494.

References

Zamir E, Geiger B, Kam Z . Quantitative multicolor compositional imaging resolves molecular domains in cell-matrix adhesions. PLoS One. 2008; 3(4):e1901. PMC: 2270910. DOI: 10.1371/journal.pone.0001901. View

Butler B, Gao C, Mersich A, Blystone S . Purified integrin adhesion complexes exhibit actin-polymerization activity. Curr Biol. 2006; 16(3):242-51. DOI: 10.1016/j.cub.2005.12.033. View

Discher D, Janmey P, Wang Y . Tissue cells feel and respond to the stiffness of their substrate. Science. 2005; 310(5751):1139-43. DOI: 10.1126/science.1116995. View

Gingras A, Bate N, Goult B, Hazelwood L, Canestrelli I, Grossmann J . The structure of the C-terminal actin-binding domain of talin. EMBO J. 2007; 27(2):458-69. PMC: 2168396. DOI: 10.1038/sj.emboj.7601965. View

Blummel J, Perschmann N, Aydin D, Drinjakovic J, Surrey T, Lopez-Garcia M . Protein repellent properties of covalently attached PEG coatings on nanostructured SiO(2)-based interfaces. Biomaterials. 2007; 28(32):4739-47. DOI: 10.1016/j.biomaterials.2007.07.038. View

Shemesh T, Geiger B, Bershadsky A, Kozlov M . Focal adhesions as mechanosensors: a physical mechanism. Proc Natl Acad Sci U S A. 2005; 102(35):12383-8. PMC: 1194898. DOI: 10.1073/pnas.0500254102. View

Cukierman E, Pankov R, Stevens D, Yamada K . Taking cell-matrix adhesions to the third dimension. Science. 2001; 294(5547):1708-12. DOI: 10.1126/science.1064829. View

Ussar S, Wang H, Linder S, Fassler R, Moser M . The Kindlins: subcellular localization and expression during murine development. Exp Cell Res. 2006; 312(16):3142-51. DOI: 10.1016/j.yexcr.2006.06.030. View

Cavalcanti-Adam E, Volberg T, Micoulet A, Kessler H, Geiger B, Spatz J . Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys J. 2007; 92(8):2964-74. PMC: 1831685. DOI: 10.1529/biophysj.106.089730. View

10.

Vogel V . Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu Rev Biophys Biomol Struct. 2006; 35:459-88. DOI: 10.1146/annurev.biophys.35.040405.102013. View

11.

Calderwood D . Integrin activation. J Cell Sci. 2004; 117(Pt 5):657-66. DOI: 10.1242/jcs.01014. View

12.

Papagrigoriou E, Gingras A, Barsukov I, Bate N, Fillingham I, Patel B . Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle. EMBO J. 2004; 23(15):2942-51. PMC: 514914. DOI: 10.1038/sj.emboj.7600285. View

13.

Grosheva I, Vittitow J, Goichberg P, Gabelt B, Kaufman P, Borras T . Caldesmon effects on the actin cytoskeleton and cell adhesion in cultured HTM cells. Exp Eye Res. 2006; 82(6):945-58. DOI: 10.1016/j.exer.2006.01.006. View

14.

Loer B, Bauer R, Bornheim R, Grell J, Kremmer E, Kolanus W . The NHL-domain protein Wech is crucial for the integrin-cytoskeleton link. Nat Cell Biol. 2008; 10(4):422-8. DOI: 10.1038/ncb1704. View

15.

Zhang X, Jiang G, Cai Y, Monkley S, Critchley D, Sheetz M . Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat Cell Biol. 2009; 10(9):1062-8. PMC: 2746969. DOI: 10.1038/ncb1765. View

16.

Lock J, Wehrle-Haller B, Stromblad S . Cell-matrix adhesion complexes: master control machinery of cell migration. Semin Cancer Biol. 2007; 18(1):65-76. DOI: 10.1016/j.semcancer.2007.10.001. View

17.

Ballestrem C, Hinz B, Imhof B, Wehrle-Haller B . Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior. J Cell Biol. 2002; 155(7):1319-32. PMC: 2199321. DOI: 10.1083/jcb.200107107. View

18.

Chen C, Mrksich M, Huang S, Whitesides G, Ingber D . Geometric control of cell life and death. Science. 1997; 276(5317):1425-8. DOI: 10.1126/science.276.5317.1425. View

19.

Arthur W, Petch L, Burridge K . Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. Curr Biol. 2000; 10(12):719-22. DOI: 10.1016/s0960-9822(00)00537-6. View

20.

Zaidel-Bar R, Ballestrem C, Kam Z, Geiger B . Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J Cell Sci. 2003; 116(Pt 22):4605-13. DOI: 10.1242/jcs.00792. View