Crawling Toward a Unified Model of Cell Motility: Spatial and Temporal Regulation of Actin Dynamics

Abstract

Crawling cells of various morphologies displace themselves in their biological environments by a similar overall mechanism of protrusion through actin assembly at the front coordinated with retraction at the rear. Different cell types organize very distinct protruding structures, yet they do so through conserved biochemical mechanisms to regulate actin polymerization dynamics and vary the mechanical properties of these structures. The moving cell must spatially and temporally regulate the biochemical interactions of its protein components to exert control over higher-order dynamic structures created by these proteins and global cellular responses four or more orders of magnitude larger in scale and longer in time than the individual protein-protein interactions that comprise them. To fulfill its biological role, a cell globally responds with high sensitivity to a local perturbation or signal and coordinates its many intracellular actin-based functional structures with the physical environment it experiences to produce directed movement. This review attempts to codify some unifying principles for cell motility that span organizational scales from single protein polymer filaments to whole crawling cells.

Tropomodulin Binds Two Tropomyosins: A Novel Model for Actin Filament Capping

“…9 % polyacrylamide gels that were polymerized in the presence of 10% glycerol without SDS were used (24). To prepare complexes for loading onto gels, equimolar amounts of Tmod in the absence or presence of GlyTM1b [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Zip were mixed in a 1:2 molar ratio. For titration, stock solutions of tropomodulin and GlyTM1b [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Zip were mixed in different ratios in buffer containing 100 mM NaCl.…”

Stochastic models of intracellular transport

“…One of the challenges in cellular biology is understanding how the coupling of diffusive or vesicular transport with chemical reactions and cell signaling generates self-organizing structures within a cell. One clear example is given by the actin and microtubular cytoskeletons, which not only provide tracks for intracellular transport, but also determine cell shape and polarity (Lacayo et al, 2007), drive cell motility (Mogilner and Edelstein-Keshet, 2002;Rafelski and Theriot, 2004), and form the spindle apparatus during cell division (Eggert et al, 2006;Glotzer, 2009). Self-organization of the cytoskeleton and its regulation by cell signaling also plays a crucial role in axonal growth and guidance during neurogenesis and cortical development (Goldberg, 2003;Graham et al, 2006;Suter and Miller, 2011).…”

Discontinuous fluidization transition in time-correlated assemblies of actively deforming particles

“…Such tissues display a surprisingly fast and collective dynamics, which would not take place under equilibrium conditions [10]. This dynamics has been ascribed to at least three distinct active processes [13]: (i) self-propulsion through cell motility such as crawling [15], (ii) self-deformation through protrusion and contraction [16][17][18], and (iii) cell division and apoptosis [14]. The vertex model for tissues [12,19,20] includes the first two of these active processes and predicts a continuous static transition from an arrested to a flowing state [21].…”