How do actin filaments transmit force?2018-02-06T13:23:43+08:30

How do actin filaments act as a force-sensing conduit for both internal and external forces?

Internal forces

The orientation of individual actin filaments in the cytoskeleton is a force-driven evolutionary process [1] that contributes to the elastic behavior of the network and influences whether a filament will deform by compression, bending or extension [2][3]. Cross-linked actin networks initially become more elastic under low force as a result of filament resistance to the direction of compression [4]. As the force increases, individual filaments inherently resist being compressed and/or cross-linking proteins become more extended, which causes the cytoskeleton network to become more rigid [5][6]; cell stiffening has also been correlated with actin recruitment [7]. Each of these processes in turn, can influence mechanosensors that are linked to the actin network to induce subsequent mechanotransduction events. Although forces ~ 400 pN along the filament axis will break actin filaments, much higher forces are generated in migrating cells (reviewed in [8] ); this raises the question – how does a cell alleviate the forces on the internal actin network?? The answer lies in the proteins that are linked to the actin: extreme stress on the filaments causes buckling and reduced elasticity of the network in a process known as ‘stress softening’ [9]. Softening is attributed to either filament fracturing, which leads to new uncapped ends for filament assembly/disassembly, or to softening, which may be due to unbinding of flexible protein crosslinkers [4][10]. In addition, because the filaments are interconnected to the rest of the cytoskeleton, buckled filaments don’t collapse and the process can be reversed when the stress is removed [11] (reviewed in [12][13]).

External or applied forces

The actin cytoskeleton is physically connected with the cell exterior, e.g., ECM or other cells, through a multiprotein complex known as the focal adhesion complex. Interactions between cell surface molecules, e.g., integrins, and the actin cytoskeleton are bidirectional, with the focal adhesion complex forming the link between them [14]. Actin filaments and their associated focal adhesion complexes act as information handling machines or mechanosensors: they convert both the strength of the adhesion and the tensile forces along the linked network of actin filaments (and associated proteins) into biochemical signals that control actin extension and cell migration (reviewed in [13][15][16][17][18][19]). Focal adhesions are subject to continuous pulling forces [20][21] and the force differences due to external stress [22] or the chemical nature (reviewed in [23]), rigidity [24][25], and topography of the exterior components [26][27][28] (reviewed in [29][30][31]) will influence the assembly and organization of the actin cytoskeleton [28][32][33][34][35].

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