How do actin filaments form higher-order assemblies that produce and respond to force?2018-02-06T13:23:19+00:00

How do actin filaments form higher-order assemblies that produce and respond to force?

Many different types of cells use actin filaments to generate tensional forces and to exert traction forces on their adhesions and linked ECM (or other cells); these processes cause resting tensile force (reviewed in [1][2]). Local stress or force differences that occur both internally and externally are transduced through the actin filaments and focused onto mechanosensors throughout the interlinked system rather than being limited to local deformation (reviewed in [3]); this process leads to mechanotransduction events that influence the cell shape and/or motility (reviewed in [4]).

Cells exert traction forces on the ECM and generate tension at focal adhesions through actin stress fibers, which are higher-order structures in the cytoplasm that consist of parallel contractile bundles of actin and myosin filaments. Stress fibers are linked at their ends to the ECM through focal adhesion complexes. Cell tension is generated along the actin filaments by the movement of myosin II motor proteins along the filaments (see contractile bundles). The elasticity of the actin network appears to be inherent to actin filaments and is independent of myosin II motor activity [5]. Forces produced by the contraction of stress fibers not only helps the cell body to translocate during migration [6] [7], but they also serve as a vital “inside-out? feedback system to regulate actin filament initiation [8], cell growth and motility [9][10], and formation/maturation of focal adhesion complexes [11][12]. Forces produced by stress fibers also stabilize the cell structure and contribute to establishing the cell polarity [7] and they help determine the cell fate [13][14]. There is no evidence that forces influence stress fiber contractile activity by increasing the exchange of ADP for ATP on myosin, however, force can weakly increase the release of the myosin heads from the actin filaments (reviewed in [15]).

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  1. Ingber DE. Tensegrity-based mechanosensing from macro to micro. Prog. Biophys. Mol. Biol. 2008; 97(2-3):163-79. [PMID: 18406455]
  2. Ingber DE. Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 1997; 59:575-99. [PMID: 9074778]
  3. Gillespie PG, and Walker RG. Molecular basis of mechanosensory transduction. Nature 2001; 413(6852):194-202. [PMID: 11557988]
  4. Vogel V. Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu Rev Biophys Biomol Struct 2006; 35:459-88. [PMID: 16689645]
  5. Chaudhuri O, Parekh SH, and Fletcher DA. Reversible stress softening of actin networks. Nature 2007; 445(7125):295-8. [PMID: 17230186]
  6. Parker KK, Brock AL, Brangwynne C, Mannix RJ, Wang N, Ostuni E, Geisse NA, Adams JC, Whitesides GM, and Ingber DE. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces. FASEB J. 2002; 16(10):1195-204. [PMID: 12153987]
  7. Svitkina TM, Verkhovsky AB, McQuade KM, and Borisy GG. Analysis of the actin-myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J. Cell Biol. 1997; 139(2):397-415. [PMID: 9334344]
  8. Gupton SL, Eisenmann K, Alberts AS, and Waterman-Storer CM. mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. J. Cell. Sci. 2007; 120(Pt 19):3475-87. [PMID: 17855386]
  9. Vicente-Manzanares M, Zareno J, Whitmore L, Choi CK, and Horwitz AF. Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J. Cell Biol. 2007; 176(5):573-80. [PMID: 17312025]
  10. Even-Ram S, Doyle AD, Conti MA, Matsumoto K, Adelstein RS, and Yamada KM. Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk. Nat. Cell Biol. 2007; 9(3):299-309. [PMID: 17310241]
  11. Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T, Narumiya S, Kam Z, Geiger B, and Bershadsky AD. 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. 2001; 153(6):1175-86. [PMID: 11402062]
  12. Giannone G, Dubin-Thaler BJ, Rossier O, Cai Y, Chaga O, Jiang G, Beaver W, Döbereiner H, Freund Y, Borisy G, and Sheetz MP. Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 2007; 128(3):561-75. [PMID: 17289574]
  13. Griffin MA, Sen S, Sweeney HL, and Discher DE. Adhesion-contractile balance in myocyte differentiation. J. Cell. Sci. 2004; 117(Pt 24):5855-63. [PMID: 15522893]
  14. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, and Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 2004; 6(4):483-95. [PMID: 15068789]
  15. Khan S, and Sheetz MP. Force effects on biochemical kinetics. Annu. Rev. Biochem. 1997; 66:785-805. [PMID: 9242924]