Regulation and Dynamics of Force Transmission at Individual Cell-matrix Adhesion Bonds

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 May 23

PMID 32440534

Citations 44

Authors

Steven J Tan

Alice C Chang

Sarah M Anderson

Cayla M Miller

Louis S Prahl

David J Odde

Alexander R Dunn

Affiliations

Soon will be listed here.

Abstract

Integrin-based adhesion complexes link the cytoskeleton to the extracellular matrix (ECM) and are central to the construction of multicellular animal tissues. How biological function emerges from the tens to thousands of proteins present within a single adhesion complex remains unclear. We used fluorescent molecular tension sensors to visualize force transmission by individual integrins in living cells. These measurements revealed an underlying functional modularity in which integrin class controlled adhesion size and ECM ligand specificity, while the number and type of connections between integrins and F-actin determined the force per individual integrin. In addition, we found that most integrins existed in a state of near-mechanical equilibrium, a result not predicted by existing models of cytoskeletal force transduction. A revised model that includes reversible cross-links within the F-actin network can account for this result and suggests one means by which cellular mechanical homeostasis can arise at the molecular level.

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References

Morimatsu M, Mekhdjian A, Chang A, Tan S, Dunn A . Visualizing the interior architecture of focal adhesions with high-resolution traction maps. Nano Lett. 2015; 15(4):2220-8. PMC: 5924765. DOI: 10.1021/nl5047335. View

Benito-Jardon M, Klapproth S, Gimeno-LLuch I, Petzold T, Bharadwaj M, Muller D . The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes. Elife. 2017; 6. PMC: 5279944. DOI: 10.7554/eLife.22264. View

Huang D, Bax N, Buckley C, Weis W, Dunn A . Vinculin forms a directionally asymmetric catch bond with F-actin. Science. 2017; 357(6352):703-706. PMC: 5821505. DOI: 10.1126/science.aan2556. View

De Mets R, Wang I, Balland M, Oddou C, Moreau P, Fourcade B . Cellular tension encodes local Src-dependent differential β and β integrin mobility. Mol Biol Cell. 2018; 30(2):181-190. PMC: 6589565. DOI: 10.1091/mbc.E18-04-0253. View

Gardel M, Schneider I, Aratyn-Schaus Y, Waterman C . Mechanical integration of actin and adhesion dynamics in cell migration. Annu Rev Cell Dev Biol. 2009; 26:315-33. PMC: 4437624. DOI: 10.1146/annurev.cellbio.011209.122036. View

Zaidel-Bar R, Itzkovitz S, Maayan A, Iyengar R, Geiger B . Functional atlas of the integrin adhesome. Nat Cell Biol. 2007; 9(8):858-67. PMC: 2735470. DOI: 10.1038/ncb0807-858. View

Brown C, Hebert B, Kolin D, Zareno J, Whitmore L, Horwitz A . Probing the integrin-actin linkage using high-resolution protein velocity mapping. J Cell Sci. 2006; 119(Pt 24):5204-14. DOI: 10.1242/jcs.03321. View

Hu K, Ji L, Applegate K, Danuser G, Waterman-Storer C . Differential transmission of actin motion within focal adhesions. Science. 2007; 315(5808):111-5. DOI: 10.1126/science.1135085. View

Beroz F, Jawerth L, Munster S, Weitz D, Broedersz C, Wingreen N . Physical limits to biomechanical sensing in disordered fibre networks. Nat Commun. 2017; 8:16096. PMC: 5520107. DOI: 10.1038/ncomms16096. View

10.

Elosegui-Artola A, Oria R, Chen Y, Kosmalska A, Perez-Gonzalez C, Castro N . Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nat Cell Biol. 2016; 18(5):540-8. DOI: 10.1038/ncb3336. View

11.

Schiller H, Hermann M, Polleux J, Vignaud T, Zanivan S, Friedel C . β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat Cell Biol. 2013; 15(6):625-36. DOI: 10.1038/ncb2747. View

12.

Hoffmann J, Fermin Y, Stricker R, Ickstadt K, Zamir E . Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol. Elife. 2014; 3:e02257. PMC: 4040925. DOI: 10.7554/eLife.02257. View

13.

Mendoza M, Besson S, Danuser G . Quantitative fluorescent speckle microscopy (QFSM) to measure actin dynamics. Curr Protoc Cytom. 2012; Chapter 2:Unit2.18. PMC: 3688286. DOI: 10.1002/0471142956.cy0218s62. View

14.

Bangasser B, Rosenfeld S, Odde D . Determinants of maximal force transmission in a motor-clutch model of cell traction in a compliant microenvironment. Biophys J. 2013; 105(3):581-92. PMC: 3736748. DOI: 10.1016/j.bpj.2013.06.027. View

15.

Toplak T, Pandzic E, Chen L, Vicente-Manzanares M, Horwitz A, Wiseman P . STICCS reveals matrix-dependent adhesion slipping and gripping in migrating cells. Biophys J. 2012; 103(8):1672-82. PMC: 3475391. DOI: 10.1016/j.bpj.2012.08.060. View

16.

Ye F, Lagarrigue F, Ginsberg M . SnapShot: talin and the modular nature of the integrin adhesome. Cell. 2014; 156(6):1340-1340.e1. PMC: 4479492. DOI: 10.1016/j.cell.2014.02.048. View

17.

Geiger T, Zaidel-Bar R . Opening the floodgates: proteomics and the integrin adhesome. Curr Opin Cell Biol. 2012; 24(5):562-8. DOI: 10.1016/j.ceb.2012.05.004. View

18.

Elosegui-Artola A, Bazellieres E, Allen M, Andreu I, Oria R, Sunyer R . Rigidity sensing and adaptation through regulation of integrin types. Nat Mater. 2014; 13(6):631-7. PMC: 4031069. DOI: 10.1038/nmat3960. View

19.

Xu J, Tseng Y, Wirtz D . Strain hardening of actin filament networks. Regulation by the dynamic cross-linking protein alpha-actinin. J Biol Chem. 2000; 275(46):35886-92. DOI: 10.1074/jbc.M002377200. View

20.

Chang A, Mekhdjian A, Morimatsu M, Denisin A, Pruitt B, Dunn A . Single Molecule Force Measurements in Living Cells Reveal a Minimally Tensioned Integrin State. ACS Nano. 2016; 10(12):10745-10752. PMC: 5886374. DOI: 10.1021/acsnano.6b03314. View