Advent of complex flows in epithelial tissues.

The collective migration of cells in tissue pervades many important biological processes, such as wound healing, organism development, and cancer metastasis. Recent experiments on wound healing show that the collective migratory behavior of cells can be quite complex, including transient vortices and long-range correlations. Here, we explore cellular flows in epithelial tissues using a model that considers the force distribution and polarity of a single cell along with cell-cell adhesion. We show that the dipole nature of a crawling cell's force distribution destabilizes steady cellular motion. We determine the values of the physical parameters that are necessary to produce these complex motions and use numerical simulation to verify the linear analysis and to demonstrate the complex flows. We find that the tendency for cells to align is the dominant physical parameter that determines the stability of steady flows in the epithelium.

[1]  R. Goldstein,et al.  Self-concentration and large-scale coherence in bacterial dynamics. , 2004, Physical review letters.

[2]  Mark Zajac,et al.  The moving boundary node method: A level set-based, finite volume algorithm with applications to cell motility , 2010, J. Comput. Phys..

[3]  F. Saltel,et al.  The mechanisms and dynamics of αvβ3 integrin clustering in living cells , 2005, The Journal of cell biology.

[4]  Gabriel Fenteany,et al.  Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets , 2000, Current Biology.

[5]  S. Leibler,et al.  Porters versus rowers: a unified stochastic model of motor proteins , 1993, The Journal of cell biology.

[6]  Daniel Choquet,et al.  Nucleation and growth of cadherin adhesions. , 2007, Experimental cell research.

[7]  M. Poujade,et al.  Velocity fields in a collectively migrating epithelium. , 2010, Biophysical journal.

[8]  P. Chavrier,et al.  Collective migration of an epithelial monolayer in response to a model wound , 2007, Proceedings of the National Academy of Sciences.

[9]  Miguel Vicente-Manzanares,et al.  Actin and α-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner , 2008, Nature Cell Biology.

[10]  Rizwan U. Farooqui,et al.  Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement , 2005, Journal of Cell Science.

[11]  Willy Supatto,et al.  Dynamic Analyses of Drosophila Gastrulation Provide Insights into Collective Cell Migration , 2008, Science.

[12]  Chun-Min Lo,et al.  Nonmuscle myosin IIb is involved in the guidance of fibroblast migration. , 2003, Molecular biology of the cell.

[13]  C. Wolgemuth Collective swimming and the dynamics of bacterial turbulence. , 2008, Biophysical journal.

[14]  M. Shelley,et al.  Instabilities and pattern formation in active particle suspensions: kinetic theory and continuum simulations. , 2008, Physical review letters.

[15]  Sriram Ramaswamy,et al.  Hydrodynamic fluctuations and instabilities in ordered suspensions of self-propelled particles. , 2001, Physical review letters.

[16]  Micah Dembo,et al.  Rho mediates the shear-enhancement of endothelial cell migration and traction force generation. , 2004, Biophysical journal.

[17]  Andrew D. Doyle,et al.  Simultaneous, real-time imaging of intracellular calcium and cellular traction force production. , 2002, BioTechniques.

[18]  R. Austin,et al.  Force mapping in epithelial cell migration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Alessandra Boletta,et al.  Polycystin-1 induces cell migration by regulating phosphatidylinositol 3-kinase-dependent cytoskeletal rearrangements and GSK3beta-dependent cell cell mechanical adhesion. , 2007, Molecular biology of the cell.

[20]  Tomaz Velnar,et al.  The Wound Healing Process: An Overview of the Cellular and Molecular Mechanisms , 2009, The Journal of international medical research.

[21]  Pilhwa Lee,et al.  Crawling Cells Can Close Wounds without Purse Strings or Signaling , 2011, PLoS Comput. Biol..

[22]  Sean X. Sun,et al.  A mechanical model of actin stress fiber formation and substrate elasticity sensing in adherent cells , 2010, Proceedings of the National Academy of Sciences.

[23]  P. Friedl,et al.  Collective cell migration in morphogenesis and cancer. , 2004, The International journal of developmental biology.

[24]  M. Dembo,et al.  Stresses at the cell-to-substrate interface during locomotion of fibroblasts. , 1999, Biophysical journal.