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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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Cell-migration in two-state micropatterns

TL;DR: An artificial micrometre-scale two-state system for the study of cell migration in confinement is developed and it is established that highly metastatic MDA-MB-231 breast cancer cells and non-tumourigenic MCF10A breast epithelial cells have distinct deterministic dynamics on two- state patterns with a bridge width of 7.2 μm.
Posted ContentDOI

Inference of Granger-causal relations in molecular systems -- a case study of the functional hierarchy among actin regulators in lamellipodia

TL;DR: In this article, the Granger-causal inference of functional cause-effect relations among actin regulators, using the constitutive image fluctuations reporting regulator recruitment / activation as the input, is presented.
Journal ArticleDOI

Interferometric fluorescence cross correlation spectroscopy

TL;DR: A method utilizing single photon interference and fluorescence correlation spectroscopy (FCS) to simultaneously measure transport of fluorescent molecules within aqueous samples is presented and validated by measuring transport of quantum dots, associated with VSV-G receptor along cellular membranes as well as within viscous gels.

Role of cytoskeletal remodeling in T cell receptor signaling and integrin activation at the immunological synapse

TL;DR: It is demonstrated that F-actin flow is largely driven by actin polymerization, rather than by myosin IIA contraction, and that ongoing remodeling of actin cytoskeleton is required to sustain signaling and to choreograph spatio-temporal organization of receptors and their associated complexes at the IS during early phases of T cell activation.
Posted ContentDOI

IGF1R undergoes active and directed centripetal transport on filopodia upon receptor activation

TL;DR: Results show that IGF1R can move directionally on the plasma membrane protrusions, supporting a sensory role for filopodia in interpreting local IGF1 gradients.
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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