BIOMIMETIC SYSTEMS SHED LIGHT ON ACTIN-BASED MOTILITY DOWN TO THE MOLECULAR SCALE (original) (raw)
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Actin Dynamics, Architecture, and Mechanics in Cell Motility
Physiological Reviews, 2014
Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles.
Filament capping and nucleation in actin-based motility
The European Physical Journal Special Topics, 2010
Propulsion by actin polymerization is versatilely used in cell motility. Here, we investigate a model of the semi-flexible region of an actin gel close to a propelled object describing the force generation, the dynamics of the propagation velocity, filament attachment to and detachment from the obstacle surface and dynamics of the number of filaments, which result from filament nucleation and capping. The model equations are derived as moment equations of the length distributions. We find a variety of dynamic regimes. The filament number may respond very sensitively to small changes of the attachment rate.
Cell motility driven by actin polymerization
Biophysical Journal, 1996
Certain kinds of cellular movements are apparently driven by actin polymerization. Examples include the lamellipodia of spreading and migrating embryonic cells, and the bacterium Listeria monocytogenes, that propels itself through its host's cytoplasm by constructing behind it a polymerized tail of cross-linked actin filaments. Peskin et al. (1993) formulated a model to explain how a polymerizing filament could rectify the Brownian motion of an object so as to produce unidirectional force (Peskin, C., G. Odell, and G. Oster. 1993. Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys. J. 65:316-324). Their "Brownian ratchet" model assumed that the filament was stiff and that thermal fluctuations affected only the "load," i.e., the object being pushed. However, under many conditions of biological interest, the thermal fluctuations of the load are insufficient to produce the observed motions. Here we shall show that the thermal motions of the polymerizing filaments can produce a directed force. This "elastic Brownian ratchet" can explain quantitatively the propulsion of Listeria and the protrusive mechanics of lamellipodia. The model also explains how the polymerization process nucleates the orthogonal structure of the actin network in lamellipodia.
2007
Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, move inside the infected cells by riding on an actin tail. The actin tail is formed from highly crosslinked polymerizing actin filaments, which undergo cycles of attachment and detachment to and from the surface of bacteria. In this thesis, we formulated a simple theoretical model of actin-based motility. The physical mechanism for our model is based on the load-dependent detachment rate, the load-dependent polymerization velocity, the restoring force of attached filaments, the pushing force of detached filaments and finally on the cross-linkage and/or entanglement of the filament network. We showed that attachment and detachment of filaments to the obstacle, as well as polymerization and cross-linking of the filaments lead to spontaneous oscillations in obstacle velo...
Mechanism of Actin-Based Motility: A Dynamic State Diagram
Biophysical Journal, 2005
Cells move by a dynamical reorganization of their cytoskeleton, orchestrated by a cascade of biochemical reactions directed to the membrane. Designed objects or bacteria can hijack this machinery to undergo actin-based propulsion inside cells or in a cell-like medium. These objects can explore the dynamical regimes of actin-based propulsion, and display different regimes of motion, in a continuous or periodic fashion. We show that bead movement can switch from one regime to the other, by changing the size of the beads or the surface concentration of the protein activating actin polymerization. We experimentally obtain the state diagram of the bead dynamics, in which the transitions between the different regimes can be understood by a theoretical approach based on an elastic force opposing a friction force. Moreover, the experimental characteristics of the movement, such as the velocity and the characteristic times of the periodic movement, are predicted by our theoretical analysis.
New Proposed Mechanism of Actin-Polymerization-Driven Motility
Biophysical Journal, 2008
We present the first numerical simulation of actin-driven propulsion by elastic filaments. Specifically, we use a Brownian dynamics formulation of the dendritic nucleation model of actin-driven propulsion. We show that the model leads to a self-assembled network that exerts forces on a disk and pushes it with an average speed. This simulation approach is the first to observe a speed that varies nonmonotonically with the concentration of branching proteins (Arp2/3), capping protein, and depolymerization rate, in accord with experimental observations. Our results suggest a new interpretation of the origin of motility. When we estimate the speed that this mechanism would produce in a system with realistic rate constants and concentrations as well as fluid flow, we obtain a value that is within an order-of-magnitude of the polymerization speed deduced from experiments.