Force propagation across cells: mechanical coherence of dynamic cytoskeletons

Abstract

A critical function of cells is to provide a force-bearing linkage from matrix to matrix, matrix to cells, or from cell to cell in a tissue and organ as well as a force generating structure. In fully differentiated skin cells, much of the force is borne by intermediate filaments. In dynamic tissues or isolated cells on matrix, high forces are generated by myosin II pulling on actin, either through stress fibers or through some other trans-cytoplasmic network. In epithelia, myosin II clearly plays a critical role in forming a contractile ring around wounds that provides turgor and restructuring forces. A major mystery is how a dynamic cytoskeleton can create a mechanically coherent cytoplasm. We suggest that the key lie in the continuous assembly of actin and myosin filaments in the cell periphery that has been recently found in isolated fibroblasts.

Figure 1

Myosin II forms a ring at subapical position and contracts to close the wound. (a) 5 min after laser ablation of the cells indicated by the star, a monolayer of MDCK cells were fixed and stained for F-actin. The myosin light chain (MLC)-EGFP in cells neighboring to the ablated cells forms a contractile ring at the subapical position. Note MLC is a component of myosin II; it binds to myosin II heavy chain to constitute the functional myosin II. (b) Illustration of apical-basal polarity of an epithelial cell layer. (c) Dynamics of the contraction of MLC ring in wound closure induced by laser ablation of cells. Time in minutes. Figure modified, with permission, from Tamada M, Perez TD, Nelson WJ, and Sheetz MP (2007) J Cell Biol, 176:27-33.

Figure 2

Addition of actin filament at the adhesion sites and rapid turnover of actin in stress fibers. At focal adhesions, there is active polymerization of actin filaments and crosslinking of actin filaments by α-actinin. Myosin II incorporates into the α-actinin crosslinked actin filament bundles to displace α-actinin and to contract actin bundles, generating contractile force. Consequently, focal adhesions grow in response to the contraction force. The process is extremely dynamic; there are always actin polymerization and depolymerization, myosin II assembly and disassembly, and α-actinin association and disassociation with actin filaments. Figure modified, with permission, from Hotulainen P and Lappalainen P (2006) J Cell Biol 173:383-394.