Cell-matrix adhesion plays a major role during cell migration. Proteins from adhesion structures connect the extracellular matrix to the actin cytoskeleton, allowing the growing actin network to push the plasma membrane and the contractile cables (stress fibers) to pull the cell body. Force transmission to the extracellular matrix depends on several parameters including the regulation of actin dynamics in adhesion structures, the contractility of stress fibers, and the mechanosensitive response of adhesion structures. Here we highlight recent findings on the molecular mechanisms by which actin assembly is regulated in adhesion structures and the molecular basis of the mechanosensitivity of focal adhesions. 1. Introduction In multicellular organisms, cell migration plays an essential role in a variety of physiological processes such as embryogenesis, tissue regeneration, immune response, and wound healing. The misregulation of cell migration is also responsible for many pathological processes including cancers [1]. The migratory cycle is a complex process in which actin dynamics play a central role at every step. Actin assembly drives the extension of flat membrane protrusions called lamellipodia and finger-like protrusions called filopodia to push the membrane. To anchor the protrusion, the cell front interacts with the extracellular matrix (ECM) by forming nascent adhesions (or focal complexes) that are connected to the intracellular lamellipodial actin network. Nascent adhesions can either disassemble or, in response to the actomyosin force, mature into larger structures called focal adhesions (FAs) that assemble contractile actomyosin cables (stress fibers) (Figure 1). To complete this migratory cycle, the contraction of stress fibers retracts the trailing edge [2]. In this cycle, proteins from adhesion structures connect the ECM to the actin cytoskeleton (Figure 1), allowing the growing actin network to push the plasma membrane forward and the contractile stress fibers to pull the cell body and retract the tail. Force transmission to the ECM depends on a variety of parameters including the regulation of actin dynamics in adhesion structures, the contractility of stress fibers, and the mechanosensitive response of adhesion structures [3]. Figure 1: Actin networks in cell migration and organization of nascent adhesions and focal adhesions. Left, scheme of a migrating cell displaying characteristic actin structures: lamellipodial and filopodial actin networks and the three classes of stress fibers (transverse arcs, dorsal stress fibers, ventral stress
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