Actin–myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility

Abstract

We have analyzed the spontaneous symmetry breaking and initiation of actin-based motility in keratocytes (fish epithelial cells). In stationary keratocytes, the actin network flow was inwards and radially symmetric. Immediately before motility initiation, the actin network flow increased at the prospective cell rear and reoriented in the perinuclear region, aligning with the prospective axis of movement. Changes in actin network flow at the cell front were detectable only after cell polarization. Inhibition of myosin II or Rho kinase disrupted actin network organization and flow in the perinuclear region and decreased the motility initiation frequency, whereas increasing myosin II activity with calyculin A increased the motility initiation frequency. Local stimulation of myosin activity in stationary cells by the local application of calyculin A induced directed motility initiation away from the site of stimulation. Together, these results indicate that large-scale actin–myosin network reorganization and contractility at the cell rear initiate spontaneous symmetry breaking and polarized motility of keratocytes.

Downregulation of basal myosin‐ II is required for cell shape changes and tissue invagination

“…At the tissue level, this is manifested with the lack of the characteristic apical anisotropic constricted cell shape and invagination, thus revealing the importance of apico‐basal polarization of myosin‐II activity during morphogenesis of the ventral furrow. Similarly, subcellular polarization of myosin‐II is observed also during cell migration (front‐back; Yam et al , 2007) and cytokinesis (poles–cleavage furrow; Uehara et al , 2010), and a recent study has suggested a competitive mechanism for the accumulation of actomyosin in different parts of the cell (Lomakin et al , 2015). However, at the levels of optogenetic activation employed in this study (< 2‐fold up‐regulation of Rho signaling and myosin‐II levels), we did not observe a reduction in apical myosin‐II concentration.…”

Cell biology of embryonic migration

“…However, in spontaneously polarizing cells, the contraction of the rear end actually precedes the leading edge protrusion (Chen, 1979;Dunn and Zicha, 1995;Verkhovsky et al, 1999;Yam et al, 2007). Recent quantitative analysis of spontaneous polarization in fish keratinocytes (Yam et al, 2007) suggests that cell polarization signals are initiated near the nucleus and at the cell rear rather than at the leading edge.…”

“…However, in spontaneously polarizing cells, the contraction of the rear end actually precedes the leading edge protrusion (Chen, 1979;Dunn and Zicha, 1995;Verkhovsky et al, 1999;Yam et al, 2007). Recent quantitative analysis of spontaneous polarization in fish keratinocytes (Yam et al, 2007) suggests that cell polarization signals are initiated near the nucleus and at the cell rear rather than at the leading edge. Since during development the migratory cell types are often not polarized at all before the initiation of the migration at the tissue and organismal level, it appears highly likely that polarization signals in situ may originate at different cell locations to define the leading and trailing edge, and that multiple mechanisms may exist to ensure that this polarization occurs promptly, uniformly, and unambiguously in all cells of the migrating layer.…”

Damped and persistent oscillations in a simple model of cell crawling

“…Other studies [3,5,6] have focused on the fish keratocyte, which may exhibit steady gliding motions. The recent modelling paper by Herant & Dembo [7] describes a poroelastic continuum mechanical model of cell locomotion that can exhibit impressive simulations of either oscillatory ('fibroblast-like') motion or smooth ('keratocyte-like') motion.…”