A model for intracellular actin waves explored by nonlinear local perturbation analysis.

Waves and dynamic patterns in chemical and physical systems have long interested experimentalists and theoreticians alike. Here we investigate a recent example within the context of cell biology, where waves of actin (a major component of the cytoskeleton) and its regulators (nucleation promoting factors, NPFs) are observed experimentally. We describe and analyze a minimal reaction diffusion model depicting the feedback between signalling proteins and filamentous actin (F-actin). Using numerical simulation, we show that this model displays a rich variety of patterning regimes. A relatively recent nonlinear stability method, the Local Perturbation Analysis (LPA), is used to map the parameter space of this model and explain the genesis of patterns in various linear and nonlinear patterning regimes. We compare our model for actin waves to others in the literature, and focus on transitions between static polarization, transient waves, periodic wave trains, and reflecting waves. We show, using LPA, that the spatially distributed model gives rise to dynamics that are absent in the kinetics alone. Finally, we show that the width and speed of the waves depend counter-intuitively on parameters such as rates of NPF activation, negative feedback, and the F-actin time scale.

[1]  P. Maini,et al.  Spatial pattern formation in chemical and biological systems , 1997 .

[2]  Konstantin Doubrovinski,et al.  Cytoskeletal waves in the absence of molecular motors , 2008 .

[3]  Brian D. Slaughter,et al.  Weakly nonlinear analysis of symmetry breaking in cell polarity models , 2012, Physical Biology.

[4]  S. Whitelam,et al.  Transformation from spots to waves in a model of actin pattern formation. , 2008, Physical review letters.

[5]  Pablo A Iglesias,et al.  Biased excitable networks: how cells direct motion in response to gradients. , 2012, Current opinion in cell biology.

[6]  Leah Edelstein-Keshet,et al.  How Cells Integrate Complex Stimuli: The Effect of Feedback from Phosphoinositides and Cell Shape on Cell Polarization and Motility , 2012, PLoS Comput. Biol..

[7]  Richard A. Firtel,et al.  Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement , 2004, The Journal of cell biology.

[8]  J. Langer,et al.  Pattern formation in nonequilibrium physics , 1999 .

[9]  A. Zhabotinsky,et al.  Pattern formation arising from interactions between Turing and wave instabilities , 2002 .

[10]  G. Gerisch Self-organizing actin waves that simulate phagocytic cup structures , 2010, PMC biophysics.

[11]  Gaudenz Danuser,et al.  Coordination of Rho GTPase activities during cell protrusion , 2009, Nature.

[12]  Zhen Jin,et al.  Spatiotemporal complexity of a ratio-dependent predator-prey system. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[13]  L Edelstein-Keshet,et al.  Regimes of wave type patterning driven by refractory actin feedback: transition from static polarization to dynamic wave behaviour , 2012, Physical biology.

[14]  A. Turing The chemical basis of morphogenesis , 1952, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.

[15]  Alexandra Jilkine,et al.  Mathematical Model for Spatial Segregation of the Rho-Family GTPases Based on Inhibitory Crosstalk , 2007, Bulletin of mathematical biology.

[16]  J. Murray A Pre-pattern formation mechanism for animal coat markings , 1981 .

[17]  C. Abram,et al.  The ins and outs of leukocyte integrin signaling. , 2009, Annual review of immunology.

[18]  M. G. Vicker F‐actin assembly in Dictyostelium cell locomotion and shape oscillations propagates as a self‐organized reaction–diffusion wave , 2002, FEBS letters.

[19]  Andre Levchenko,et al.  Modelling Cell Polarization Driven by Synthetic Spatially Graded Rac Activation , 2012, PLoS Comput. Biol..

[20]  V. Grieneisen,et al.  Dynamics of auxin patterning in plant morphogenesis - A multilevel model study , 2009 .

[21]  Willy Govaerts,et al.  MATCONT: A MATLAB package for numerical bifurcation analysis of ODEs , 2003, TOMS.

[22]  E. Manser,et al.  Rho GTPases and their role in organizing the actin cytoskeleton , 2011, Journal of Cell Science.

[23]  Richard A. Firtel,et al.  G protein–independent Ras/PI3K/F-actin circuit regulates basic cell motility , 2007, The Journal of cell biology.

[24]  E. Hill Journal of Theoretical Biology , 1961, Nature.

[25]  Wolfgang Losert,et al.  Cell Shape Dynamics: From Waves to Migration , 2011, PLoS Comput. Biol..

[26]  F. Rivero,et al.  Rho GTPases , 2012, Methods in Molecular Biology.

[27]  David A. Calderwood,et al.  Integrins and Actin Filaments: Reciprocal Regulation of Cell Adhesion and Signaling* , 2000, The Journal of Biological Chemistry.

[28]  M. G. Vicker,et al.  Eukaryotic cell locomotion depends on the propagation of self-organized reaction-diffusion waves and oscillations of actin filament assembly. , 2002, Experimental cell research.

[29]  Alexandra Jilkine,et al.  Polarization and Movement of Keratocytes: A Multiscale Modelling Approach , 2006, Bulletin of mathematical biology.

[30]  A. Ridley Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. , 2006, Trends in cell biology.

[31]  Alexandra Jilkine,et al.  Wave-pinning and cell polarity from a bistable reaction-diffusion system. , 2008, Biophysical journal.

[32]  明 大久保,et al.  Diffusion and ecological problems : mathematical models , 1980 .

[33]  Hezi Yizhaq,et al.  Banded vegetation: biological productivity and resilience , 2005 .

[34]  W. Keith Nicholson Linear Algebra with Applications , 1986 .

[35]  P. De Camilli,et al.  Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations , 2013, Proceedings of the National Academy of Sciences.

[36]  M. Cross,et al.  Pattern formation outside of equilibrium , 1993 .

[37]  J. L. Jackson,et al.  Dissipative structure: an explanation and an ecological example. , 1972, Journal of theoretical biology.

[38]  Zhenbiao Yang,et al.  RHO Gtpases and the Actin Cytoskeleton , 2000 .

[39]  A. Carlsson,et al.  Actin dynamics: from nanoscale to microscale. , 2010, Annual review of biophysics.

[40]  Pablo A Iglesias,et al.  Cells navigate with a local-excitation, global-inhibition-biased excitable network , 2010, Proceedings of the National Academy of Sciences.

[41]  Y. Nishiura Global Structure of Bifurcating Solutions of Some Reaction-Diffusion Systems , 1982 .

[42]  K. Kruse,et al.  Cell motility resulting from spontaneous polymerization waves. , 2011, Physical review letters.

[43]  Alexandra Jilkine,et al.  Asymptotic and Bifurcation Analysis of Wave-Pinning in a Reaction-Diffusion Model for Cell Polarization , 2010, SIAM J. Appl. Math..

[44]  Michael J. Ward,et al.  A Metastable Spike Solution for a Nonlocal Reaction-Diffusion Model , 2000, SIAM J. Appl. Math..

[45]  Leah Edelstein-Keshet,et al.  Phosphoinositides and Rho proteins spatially regulate actin polymerization to initiate and maintain directed movement in a one-dimensional model of a motile cell. , 2007, Biophysical journal.

[46]  S. Diez,et al.  Propagating waves separate two states of actin organization in living cells , 2009, HFSP journal.

[47]  Marc W Kirschner,et al.  An Actin-Based Wave Generator Organizes Cell Motility , 2007, PLoS biology.

[48]  O. Weiner,et al.  Neutrophils Establish Rapid and Robust WAVE Complex Polarity in an Actin-Dependent Fashion , 2009, Current Biology.

[49]  S. Diez,et al.  Dynamic Actin Patterns and Arp2/3 Assembly at the Substrate-Attached Surface of Motile Cells , 2004, Current Biology.

[50]  A. Carlsson,et al.  Dendritic actin filament nucleation causes traveling waves and patches. , 2010, Physical review letters.

[51]  The chemical theory of morphogenesis , 2011 .

[52]  Till Bretschneider,et al.  The three-dimensional dynamics of actin waves, a model of cytoskeletal self-organization. , 2009, Biophysical journal.

[53]  C. Cosner,et al.  Spatial Ecology via Reaction-Diffusion Equations , 2003 .

[54]  Jingsong Xu,et al.  Divergent Signals and Cytoskeletal Assemblies Regulate Self-Organizing Polarity in Neutrophils , 2003, Cell.

[55]  Till Bretschneider,et al.  Mobile actin clusters and traveling waves in cells recovering from actin depolymerization. , 2004, Biophysical journal.

[56]  Georg R. Walther,et al.  Deterministic Versus Stochastic Cell Polarisation Through Wave-Pinning , 2012, Bulletin of mathematical biology.