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Two distinct actin networks drive the protrusion of migrating cells

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TLDR
Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks.
Abstract
Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks. A lamellipodium network assembled at the leading edge but completely disassembled within 1 to 3 micrometers. It was weakly coupled to the rest of the cytoskeleton and promoted the random protrusion and retraction of the leading edge. Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion.

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Citations
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Journal ArticleDOI

Mechanical and biochemical modeling of cortical oscillations in spreading cells.

TL;DR: An ordinary differential equation model is developed that generates oscillatory behavior consistent with current experimental observations inActomyosin-based cortical contractility and makes experimentally testable predictions.
Journal ArticleDOI

Force-exerting perpendicular lateral protrusions in fibroblastic cell contraction

TL;DR: Using fiber networks that serve as force sensors, authors describe a mechanism which leads to the contraction of parallel, neighbouring fibers, and the forces needed to move and align the neighbouring fibers that have relevance in understanding cancer-associated desmoplastic expansion.
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Modeling capping protein FRAP and CALI experiments reveals in vivo regulation of actin dynamics.

TL;DR: This analysis demonstrates that FRAP experiments with EGFP‐CP can be performed safely without changes in cell morphology, because, the intensity of the photobleaching beam is not high enough to produce the critical concentration of free barbed ends that will induce filament growth before diffusional replacement of EG FP‐CP occurs.
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Protein kinase C activation decreases peripheral actin network density and increases central nonmuscle myosin II contractility in neuronal growth cones

TL;DR: PKC activation enhances myosin II contractility in the central growth cone domain while decreasing actin density and increasing actin network flow rates in the peripheral domain, which has mechanistic implications for interpreting reported effects of PKC on growth cone guidance and neuronal regeneration.
Journal ArticleDOI

A tal(in) of cell spreading.

TL;DR: New work shows that cell spreading can be dissected into three distinct phases according to their differential requirements for talin function.
References
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Journal ArticleDOI

Cell Migration: A Physically Integrated Molecular Process

TL;DR: The authors are grateful for financial support from the National Institutes of Health (grants GM23244 and GM53905), and to very helpful comments on the manuscript from Elliot Elson, Vlodya Gelfand, Paul Matsudaira, Julie Theriot, and Sally Zigmond.
Journal ArticleDOI

Cellular Motility Driven by Assembly and Disassembly of Actin Filaments

TL;DR: A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion.
Journal ArticleDOI

The interaction of Arp2/3 complex with actin: Nucleation, high affinity pointed end capping, and formation of branching networks of filaments

TL;DR: It is shown that Arp2/3 complex purified from Acanthamoeba caps the pointed ends of actin filaments with high affinity and increases the critical concentration for polymerization at the pointed end from 0.6 to 1.0 microM.
Journal ArticleDOI

Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor

TL;DR: It is shown that exit from the cytokinetic phase of the cell cycle depends on ubiquitin-mediated proteolysis and continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components.
Journal ArticleDOI

Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone.

TL;DR: Results suggest that actin normally polymerizes at the leading edge and then flows rearward at a rate between 3-6 microns/min, which is consistent with their being secondary to effects of CB on lamellar F-actin.
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