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      Patterning and polarization of cells by intracellular flows

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          Abstract

          Beginning with Turing’s seminal work [ 1], decades of research have demonstrated the fundamental ability of biochemical networks to generate and sustain the formation of patterns. However, it is increasingly appreciated that biochemical networks both shape and are shaped by physical and mechanical processes [ 2, 3, 4]. One such process is fluid flow. In many respects, the cytoplasm, membrane and actin cortex all function as fluids, and as they flow, they drive bulk transport of molecules throughout the cell. By coupling biochemical activity to long range molecular transport, flows can shape the distributions of molecules in space. Here we review the various types of flows that exist in cells, with the aim of highlighting recent advances in our understanding of how flows are generated and how they contribute to intracellular patterning processes, such as the establishment of cell polarity.

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          Most cited references118

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          Physics of chemoreception.

          Statistical fluctuations limit the precision with which a microorganism can, in a given time T, determine the concentration of a chemoattractant in the surrounding medium. The best a cell can do is to monitor continually the state of occupation of receptors distributed over its surface. For nearly optimum performance only a small fraction of the surface need be specifically adsorbing. The probability that a molecule that has collided with the cell will find a receptor is Ns/(Ns + pi a), if N receptors, each with a binding site of radius s, are evenly distributed over a cell of radius a. There is ample room for many indenpendent systems of specific receptors. The adsorption rate for molecules of moderate size cannot be significantly enhanced by motion of the cell or by stirring of the medium by the cell. The least fractional error attainable in the determination of a concentration c is approximately (TcaD) - 1/2, where D is diffusion constant of the attractant. The number of specific receptors needed to attain such precision is about a/s. Data on bacteriophage absorption, bacterial chemotaxis, and chemotaxis in a cellular slime mold are evaluated. The chemotactic sensitivity of Escherichia coli approaches that of the cell of optimum design.
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            Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo.

            The C. elegans PAR proteins PAR-3, PAR-6, and PKC-3 are asymmetrically localized and have essential roles in cell polarity. We show that the one-cell C. elegans embryo contains a dynamic and contractile actomyosin network that appears to be destabilized near the point of sperm entry. This asymmetry initiates a flow of cortical nonmuscle myosin (NMY-2) and F-actin toward the opposite, future anterior, pole. PAR-3, PAR-6, and PKC-3, as well as non-PAR proteins that associate with the cytoskeleton, appear to be transported to the anterior by this cortical flow. In turn, PAR-3, PAR-6, and PKC-3 modulate cortical actomyosin dynamics and promote cortical flow. PAR-2, which localizes to the posterior cortex, inhibits NMY-2 from accumulating at the posterior cortex during flow, thus maintaining asymmetry by preventing inappropriate, posterior-directed flows. Similar actomyosin flows accompany the establishment of PAR asymmetries that form after the one-cell stage, suggesting that actomyosin-mediated cortical flows have a general role in PAR asymmetry.
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              Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration.

              Little is known about how neutrophils and other cells establish a single zone of actin assembly during migration. A widespread assumption is that the leading edge prevents formation of additional fronts by generating long-range diffusible inhibitors or by sequestering essential polarity components. We use morphological perturbations, cell-severing experiments, and computational simulations to show that diffusion-based mechanisms are not sufficient for long-range inhibition by the pseudopod. Instead, plasma membrane tension could serve as a long-range inhibitor in neutrophils. We find that membrane tension doubles during leading-edge protrusion, and increasing tension is sufficient for long-range inhibition of actin assembly and Rac activation. Furthermore, reducing membrane tension causes uniform actin assembly. We suggest that tension, rather than diffusible molecules generated or sequestered at the leading edge, is the dominant source of long-range inhibition that constrains the spread of the existing front and prevents the formation of secondary fronts. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                8913428
                Curr Opin Cell Biol
                Curr. Opin. Cell Biol.
                Current opinion in cell biology
                0955-0674
                1879-0410
                21 November 2019
                21 November 2019
                14 January 2020
                21 November 2020
                : 62
                : 123-134
                Affiliations
                [a ]The Francis Crick Institute, London, UK
                [b ]Institute for the Physics of Living Systems, University College London, London, UK
                [c ]MRC Laboratory for Molecular Cell Biology, University College London, London, UK
                Article
                EMS85449
                10.1016/j.ceb.2019.10.005
                6968950
                31760155
                0b228638-0b9a-425d-b408-cd5507ac9e31

                This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

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                Categories
                Article

                Cell biology
                advection,cortical flow,membrane flow,actomyosin,cell polarity,self-organization
                Cell biology
                advection, cortical flow, membrane flow, actomyosin, cell polarity, self-organization

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