Furrow constriction in animal cell cytokinesis.

Cytokinesis is the process of physical cleavage at the end of cell division; it proceeds by ingression of an acto-myosin furrow at the equator of the cell. Its failure leads to multinucleated cells and is a possible cause of tumorigenesis. Here, we calculate the full dynamics of furrow ingression and predict cytokinesis completion above a well-defined threshold of equatorial contractility. The cortical acto-myosin is identified as the main source of mechanical dissipation and active forces. Thereupon, we propose a viscous active nonlinear membrane theory of the cortex that explicitly includes actin turnover and where the active RhoA signal leads to an equatorial band of myosin overactivity. The resulting cortex deformation is calculated numerically, and reproduces well the features of cytokinesis such as cell shape and cortical flows toward the equator. Our theory gives a physical explanation of the independence of cytokinesis duration on cell size in embryos. It also predicts a critical role of turnover on the rate and success of furrow constriction. Scaling arguments allow for a simple interpretation of the numerical results and unveil the key mechanism that generates the threshold for cytokinesis completion: cytoplasmic incompressibility results in a competition between the furrow line tension and the cell poles' surface tension.

[1]  G. Charras,et al.  Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity. , 2012, Blood.

[2]  J. White,et al.  Cortical flow in animal cells. , 1988, Science.

[3]  Y. Wang,et al.  Mechanism of the formation of contractile ring in dividing cultured animal cells. II. Cortical movement of microinjected actin filaments , 1990, The Journal of cell biology.

[4]  J. Tinevez,et al.  Polar actomyosin contractility destabilizes the position of the cytokinetic furrow , 2011, Nature.

[5]  G. von Dassow,et al.  Action at a distance during cytokinesis , 2009, The Journal of cell biology.

[6]  Kuan-Chung Su,et al.  Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis. , 2011, Developmental cell.

[7]  S. Grill,et al.  Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows , 2010, Nature.

[8]  P. O’Farrell,et al.  Rho-kinase Controls Cell Shape Changes during Cytokinesis , 2006, Current Biology.

[9]  Manuel Théry,et al.  Actin Network Architecture Can Determine Myosin Motor Activity , 2012, Science.

[10]  H. Butt,et al.  Comparative analysis of viscosity of complex liquids and cytoplasm of mammalian cells at the nanoscale. , 2011, Nano letters.

[11]  F. Chang,et al.  Localization of cytokinesis factors to the future cell division site by microtubule‐dependent transport , 2012, Cytoskeleton.

[12]  Karen Oegema,et al.  Structural Memory in the Contractile Ring Makes the Duration of Cytokinesis Independent of Cell Size , 2009, Cell.

[13]  M. Matsuda,et al.  Activity of Rho-family GTPases during cell division as visualized with FRET-based probes , 2003, The Journal of cell biology.

[14]  G. Charras,et al.  Analysis of turnover dynamics of the submembranous actin cortex , 2013, Molecular biology of the cell.

[15]  J. Tinevez,et al.  Role of cortical tension in bleb growth , 2009, Proceedings of the National Academy of Sciences.

[16]  M. Balasubramanian,et al.  In vitro contraction of cytokinetic ring depends on myosin II but not on actin dynamics , 2013, Nature Cell Biology.

[17]  Robert G. Parton,et al.  Cells Respond to Mechanical Stress by Rapid Disassembly of Caveolae , 2011, Cell.

[18]  J. Joanny,et al.  Generic theory of active polar gels: a paradigm for cytoskeletal dynamics , 2004, The European physical journal. E, Soft matter.

[19]  Y. Hiramoto A PHOTOGRAPHIC ANALYSIS OF PROTOPLASMIC MOVEMENT DURING CLEAVAGE IN THE SEA URCHIN EGG , 1971, Development, growth & differentiation.

[20]  Daniel A. Fletcher,et al.  Cell mechanics and the cytoskeleton , 2010, Nature.

[21]  David Pellman,et al.  Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells , 2005, Nature.

[22]  A. Nir,et al.  On the viscous deformation of biological cells under anisotropic surface tension , 1988, Journal of Fluid Mechanics.

[23]  A. Loria,et al.  The RhoGAP Domain of CYK-4 Has an Essential Role in RhoA Activation , 2012, Current Biology.

[24]  G. Batchelor,et al.  An Introduction to Fluid Dynamics , 1968 .

[25]  J. Happel,et al.  Low Reynolds number hydrodynamics , 1965 .

[26]  S. Ramaswamy,et al.  Hydrodynamics of soft active matter , 2013 .

[27]  G. von Dassow,et al.  A microtubule-dependent zone of active RhoA during cleavage plane specification , 2005, The Journal of cell biology.

[28]  L. Collinson,et al.  Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis , 2012, Nature.

[29]  Keith Burridge,et al.  RhoA is required for cortical retraction and rigidity during mitotic cell rounding , 2003, The Journal of cell biology.

[30]  D. Robinson,et al.  Balance of actively generated contractile and resistive forces controls cytokinesis dynamics. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Kai Dierkes,et al.  Monitoring actin cortex thickness in live cells. , 2013, Biophysical journal.

[32]  M. Petronczki,et al.  Cytokinesis in animal cells. , 2015, Cold Spring Harbor perspectives in biology.

[33]  W. Sullivan,et al.  Membrane traffic: a driving force in cytokinesis. , 2005, Trends in cell biology.

[34]  Jay R. Unruh,et al.  Actin depolymerization drives actomyosin ring contraction during budding yeast cytokinesis. , 2012, Developmental cell.

[35]  E. Evans,et al.  Cortical shell-liquid core model for passive flow of liquid-like spherical cells into micropipets. , 1989, Biophysical journal.

[36]  F. Jülicher,et al.  Continuum description of the cytoskeleton: ring formation in the cell cortex. , 2005, Physical review letters.

[37]  I. Mabuchi,et al.  The effect of myosin antibody on the division of starfish blastomeres , 1977, The Journal of cell biology.

[38]  M. Gonzalez-Gaitan,et al.  Spermatocyte cytokinesis requires rapid membrane addition mediated by ARF6 on central spindle recycling endosomes , 2007, Development.

[39]  Timothy J Mitchison,et al.  Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor , 2003, Science.

[40]  M. Dembo,et al.  On the mechanics of the first cleavage division of the sea urchin egg. , 1997, Experimental cell research.

[41]  Eitan Grinspun,et al.  A discrete geometric approach for simulating the dynamics of thin viscous threads , 2012, J. Comput. Phys..

[42]  M. Gardel,et al.  F-actin buckling coordinates contractility and severing in a biomimetic actomyosin cortex , 2012, Proceedings of the National Academy of Sciences.

[43]  V. Foe,et al.  Centralspindlin and chromosomal passenger complex behavior during normal and Rappaport furrow specification in echinoderm embryos , 2012, Cytoskeleton.

[44]  J. Spudich,et al.  Determinants of Myosin II Cortical Localization during Cytokinesis , 2010, Current Biology.

[45]  Anthony A. Hyman,et al.  Supporting Material : Stress Generation and Filament Turnover During Actin Ring Constriction , 2007 .

[46]  Timothy J Mitchison,et al.  Animal cytokinesis: from parts list to mechanisms. , 2006, Annual review of biochemistry.

[47]  N. Akkas On the biomechanics of cytokinesis in animal cells. , 1980, Journal of biomechanics.

[48]  Kathleen E. Rankin,et al.  Long astral microtubules uncouple mitotic spindles from the cytokinetic furrow , 2010, The Journal of cell biology.

[49]  Patterning of polar active filaments on a tense cylindrical membrane. , 2012, Physical review letters.

[50]  Yu-Li Wang,et al.  Cortical Actin Turnover during Cytokinesis Requires Myosin II , 2005, Current Biology.

[51]  Nico Stuurman,et al.  Distinct pathways control recruitment and maintenance of myosin II at the cleavage furrow during cytokinesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[52]  Y. Hiramoto A Quantitative Description of Protoplasmic Movement During Cleavage in the Sea-Urchin Egg , 1958 .

[53]  S. Ramaswamy,et al.  The actin cortex as an active wetting layer , 2013, The European Physical Journal E.

[54]  K. Dan,et al.  Tension at the surface of the dividing sea-urchin egg. , 1972, The Journal of experimental biology.

[55]  Denis Wirtz,et al.  Probing single-cell micromechanics in vivo: the microrheology of C. elegans developing embryos. , 2006, Biophysical journal.

[56]  L. Mahadevan,et al.  Non-equilibration of hydrostatic pressure in blebbing cells , 2005, Nature.

[57]  J. White,et al.  On the mechanisms of cytokinesis in animal cells. , 1983, Journal of theoretical biology.

[58]  G. Salbreux,et al.  Hydrodynamics of cellular cortical flows and the formation of contractile rings. , 2009, Physical review letters.

[59]  H. Cohen,et al.  On a nonlinear theory of elastic shells. , 1968 .

[60]  Y. Wang,et al.  Orientation and three-dimensional organization of actin filaments in dividing cultured cells , 1993, The Journal of cell biology.

[61]  Timothy J. Mitchison,et al.  Animal cell hydraulics , 2009, Journal of Cell Science.

[62]  Kozo Kaibuchi,et al.  Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase) , 1996, Science.

[63]  Pablo A. Iglesias,et al.  Deconvolution of the Cellular Force-Generating Subsystems that Govern Cytokinesis Furrow Ingression , 2012, PLoS Comput. Biol..

[64]  P. Wadsworth,et al.  Myosin-II-Dependent Localization and Dynamics of F-Actin during Cytokinesis , 2005, Current Biology.

[65]  J. Spek Oberflächenspannungsdifferenzen als eine Ursache der Zellteilung , 1918, Archiv für Entwicklungsmechanik der Organismen.

[66]  H. Greenspan,et al.  On fluid-mechanical simulations of cell division and movement. , 1978, Journal of theoretical biology.

[67]  Guillaume Charras,et al.  Actin cortex mechanics and cellular morphogenesis. , 2012, Trends in cell biology.