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      Flow Induced Symmetry Breaking in a Conceptual Polarity Model

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          Abstract

          Important cellular processes, such as cell motility and cell division, are coordinated by cell polarity, which is determined by the non-uniform distribution of certain proteins. Such protein patterns form via an interplay of protein reactions and protein transport. Since Turing’s seminal work, the formation of protein patterns resulting from the interplay between reactions and diffusive transport has been widely studied. Over the last few years, increasing evidence shows that also advective transport, resulting from cytosolic and cortical flows, is present in many cells. However, it remains unclear how and whether these flows contribute to protein-pattern formation. To address this question, we use a minimal model that conserves the total protein mass to characterize the effects of cytosolic flow on pattern formation. Combining a linear stability analysis with numerical simulations, we find that membrane-bound protein patterns propagate against the direction of cytoplasmic flow with a speed that is maximal for intermediate flow speed. We show that the mechanism underlying this pattern propagation relies on a higher protein influx on the upstream side of the pattern compared to the downstream side. Furthermore, we find that cytosolic flow can change the membrane pattern qualitatively from a peak pattern to a mesa pattern. Finally, our study shows that a non-uniform flow profile can induce pattern formation by triggering a regional lateral instability.

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          Most cited references46

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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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            Dynamics of Cdc42 network embodies a Turing-type mechanism of yeast cell polarity.

            Complex biochemical networks can be understood by identifying their principal regulatory motifs and mode of action. We model the early phase of budding yeast cellular polarization and show that the biochemical processes in the presumptive bud site comprise a Turing-type mechanism. The roles of the prototypical activator and substrate are played by GTPase Cdc42 in its active and inactive states, respectively. We demonstrate that the nucleotide cycling of Cdc42 converts cellular energy into a stable cluster of activated Cdc42. This energy drives a continuous membrane-cytoplasmic exchange of the cluster components to counteract diffusive spread of the cluster. This exchange explains why only one bud forms per cell cycle, because the winner-takes-all competition of candidate sites inevitably selects a single site.
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              Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo.

              Cell divisions that create daughter cells of different sizes are crucial for the generation of cell diversity during animal development. In such asymmetric divisions, the mitotic spindle must be asymmetrically positioned at the end of anaphase. The mechanisms by which cell polarity translates to asymmetric spindle positioning remain unclear. Here we examine the nature of the forces governing asymmetric spindle positioning in the single-cell-stage Caenorhabditis elegans embryo. To reveal the forces that act on each spindle pole, we removed the central spindle in living embryos either physically with an ultraviolet laser microbeam, or genetically by RNA-mediated interference of a kinesin. We show that pulling forces external to the spindle act on the two spindle poles. A stronger net force acts on the posterior pole, thereby explaining the overall posterior displacement seen in wild-type embryos. We also show that the net force acting on each spindle pole is under control of the par genes that are required for cell polarity along the anterior-posterior embryonic axis. Finally, we discuss simple mathematical models that describe the main features of spindle pole behaviour. Our work suggests a mechanism for generating asymmetry in spindle positioning by varying the net pulling force that acts on each spindle pole, thus allowing for the generation of daughter cells with different sizes.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                23 June 2020
                June 2020
                : 9
                : 6
                : 1524
                Affiliations
                Arnold Sommerfeld Center for Theoretical Physics (ASC) and Center for NanoScience (CeNS), Department of Physics, Ludwig-Maximilians-Universität München, Theresienstraße 37, D–80333 München, Germany; m.wigbers@ 123456physik.uni-muenchen.de (M.C.W.); fridtjof.brauns@ 123456physik.uni-muenchen.de (F.B.); c.leung@ 123456physik.uni-muenchen.de (C.Y.L.)
                Author notes
                [* ]Correspondence: frey@ 123456lmu.de
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-4732-2878
                https://orcid.org/0000-0002-6108-9278
                https://orcid.org/0000-0003-0209-1463
                https://orcid.org/0000-0001-8792-3358
                Article
                cells-09-01524
                10.3390/cells9061524
                7349905
                32585819
                6f64c475-fd50-40c6-a261-3c5083a26774
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 May 2020
                : 19 June 2020
                Categories
                Article

                symmetry breaking,cytoplasmic flow,phase-space analysis,pattern formation

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