Mechanosignaling

Are focal adhesion dynamic?

In migrating cells, turnover of adhesion components happens throughout the adhesion life cycle, with a shift in equilibrium between rates of recruitment and removal during the various stages. At the end of each step, the structure undergoes a steady state (quasi-equilibrium) for a specific length of time before it moves on to the next stage (reviewed in [1]). However, turnover of individual adhesion components occur at different rates at any given time [2][3][4][5]. Their retrograde flux depends on impinging mechanical load [5][6][7] arising from stress, substrate stiffness and cell migration [8], and therefore on their position within the focal adhesion [6][9]. Analysis of dynamic interactions between F-actin and focal adhesion component proteins in live cells reveals differential transmission of forces through transient protein-protein interactions across the layers of the focal adhesion. The efficiency hierarchically reduces from actin-binding proteins to core proteins to integrins [6].

Hence, the differential turnover rates of certain molecular complexes may function as the switch translating mechanical to chemical signals and the physical transport itself could deliver signals to the cell interior [8]. These are critical in decision-making during assembly/disassembly of adhesions [7][10] and resulting global cellular changes.

For effective cell migration, the spatial organization of focal adhesion component proteins during rapid turnover is fundamental and critical. Distinct zones of focal adhesion nucleation, stabilization and disassembly have been discovered using averaged quantitative mapping of focal adhesion dynamics [11]. These regions are polarized corresponding to the direction of movement with the zone of nucleation at the front followed by the region of large and stable adhesions and that of disassembly at the rear. Also, from front to rear, the density of focal adhesions steadily decreases and the zones inversely correlate with the centripetal actin flow.

References

1. Gardel ML, Schneider IC, Aratyn-Schaus Y, and Waterman CM. Mechanical integration of actin and adhesion dynamics in cell migration. Annu. Rev. Cell Dev. Biol. 2010; 26:315-33. [PMID: 19575647]
2. Laukaitis CM, Webb DJ, Donais K, and Horwitz AF. Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells. J. Cell Biol. 2001; 153(7):1427-40. [PMID: 11425873]
3. Ballestrem C, Hinz B, Imhof BA, and Wehrle-Haller B. Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior. J. Cell Biol. 2001; 155(7):1319-32. [PMID: 11756480]
4. Digman MA, Brown CM, Horwitz AR, Mantulin WW, and Gratton E. Paxillin dynamics measured during adhesion assembly and disassembly by correlation spectroscopy. Biophys. J. 2007; 94(7):2819-31. [PMID: 17993500]
5. Ji L, Lim J, and Danuser G. Fluctuations of intracellular forces during cell protrusion. Nat. Cell Biol. 2008; 10(12):1393-400. [PMID: 19011623]
6. Hu K, Ji L, Applegate KT, Danuser G, and Waterman-Storer CM. Differential transmission of actin motion within focal adhesions. Science 2007; 315(5808):111-5. [PMID: 17204653]
7. Wolfenson H, Bershadsky A, Henis YI, and Geiger B. Actomyosin-generated tension controls the molecular kinetics of focal adhesions. J. Cell. Sci. 2011; 124(Pt 9):1425-32. [PMID: 21486952]
8. Guo W, and Wang Y. Retrograde fluxes of focal adhesion proteins in response to cell migration and mechanical signals. Mol. Biol. Cell 2007; 18(11):4519-27. [PMID: 17804814]
9. Wolfenson H, Lubelski A, Regev T, Klafter J, Henis YI, and Geiger B. A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions. PLoS ONE 2009; 4(1):e4304. [PMID: 19172999]
10. Digman MA, Wiseman PW, Choi C, Horwitz AR, and Gratton E. Stoichiometry of molecular complexes at adhesions in living cells. Proc. Natl. Acad. Sci. U.S.A. 2009; 106(7):2170-5. [PMID: 19168634]
11. Möhl C, Kirchgessner N, Schäfer C, Hoffmann B, and Merkel R. Quantitative mapping of averaged focal adhesion dynamics in migrating cells by shape normalization. J. Cell. Sci. 2012; 125(Pt 1):155-65. [PMID: 22250204]