Actin-based motility

Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, move inside the infected cells by riding on an actin tail. The actin tail is formed from highly crosslinked polymerizing actin filaments, which undergo cycles of attachment and detachment to and from the surface of bacteria. In this thesis, we formulated a simple theoretical model of actin-based motility. The physical mechanism for our model is based on the load-dependent detachment rate, the load-dependent polymerization velocity, the restoring force of attached filaments, the pushing force of detached filaments and finally on the cross-linkage and/or entanglement of the filament network. We showed that attachment and detachment of filaments to the obstacle, as well as polymerization and cross-linking of the filaments lead to spontaneous oscillations in obstacle velocity. The velocity spike amplitudes and periods given by our model are in good agreement with those observed experimentally in Listeria. In this model, elasticity and curvature of the obstacle is not included. Future modelling will yield insight into the role of curvature and elasticity in the actin-based motility. As an important prerequisite for this model, we used analytical calculations as well as extensive Monte Carlo (MC) simulations to investigate the pushing force of detached filaments. The analysis starts with calculations of the entropic force exerted by a grafted semiflexible polymer on a rigid wall. The pushing force, which is purely entropic in origin, depends on the polymer's contour length, persistence length, orientation and eventually on the distance of the grafting point from the rigid wall. We checked the validity range of our analytical results by performing extensive Monte Carlo simulations. This was done for stiff, semiflexible and flexible filaments. In this analysis, the obstacle is always assumed to be a rigid wall. In the real experimental situations, the obstacle (such as membrane) is not rigid and performs thermal fluctuations. Further analytical calculations and MC simulations are necessary to include the elasticity of the obstacle

[1]  S. Leibler,et al.  Unbinding transitions of interacting membranes. , 1986, Physical review letters.

[2]  K. Jacobson,et al.  The fish epidermal keratocyte as a model system for the study of cell locomotion. , 1993, Symposia of the Society for Experimental Biology.

[3]  C S Peskin,et al.  Cellular motions and thermal fluctuations: the Brownian ratchet. , 1993, Biophysical journal.

[4]  J. Theriot,et al.  Shigella flexneri surface protein IcsA is sufficient to direct actin-based motility. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Magnasco,et al.  Measurement of the persistence length of polymerized actin using fluorescence microscopy. , 1993, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[6]  W. Helfrich Steric Interaction of Fluid Membranes in Multilayer Systems , 1978 .

[7]  Nobuhiko Saitô,et al.  The Statistical Mechanical Theory of Stiff Chains , 1967 .

[8]  Linear response of a grafted semiflexible polymer to a uniform force field. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[9]  P. Chaikin,et al.  Measurement of the elasticity of the actin tail of Listeria monocytogenes , 2000, European Biophysics Journal.

[10]  J A Theriot,et al.  Motility of ActA protein-coated microspheres driven by actin polymerization. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Cossart,et al.  Actin-based motility of vaccinia virus , 1995, Nature.

[12]  J. Small,et al.  Actin filament organization in the fish keratocyte lamellipodium , 1995, The Journal of cell biology.

[13]  George Oster,et al.  Force generation by actin polymerization II: the elastic ratchet and tethered filaments. , 2003, Biophysical journal.

[14]  T. Svitkina,et al.  Actin machinery: pushing the envelope. , 2000, Current opinion in cell biology.

[15]  Hans G. Othmer,et al.  A continuum model of motility in ameboid cells , 2004, Bulletin of mathematical biology.

[16]  D. Purich,et al.  Listeria and Shigella actin-based motility in host cells. , 1998, Transactions of the American Clinical and Climatological Association.

[17]  T. L. Hill,et al.  Microfilament or microtubule assembly or disassembly against a force. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Reinhard Lipowsky,et al.  The conformation of membranes , 1991, Nature.

[19]  P. Chaikin,et al.  An elastic analysis of Listeria monocytogenes propulsion. , 2000, Biophysical journal.

[20]  Depinning of semiflexible polymers. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[21]  Frey,et al.  Force-Extension Relation and Plateau Modulus for Wormlike Chains. , 1996, Physical review letters.

[22]  T. Mitchison,et al.  Actin dynamics in vivo. , 1997, Current opinion in cell biology.

[23]  A. Carlsson Growth velocities of branched actin networks. , 2003, Biophysical journal.

[24]  Rudolf Podgornik,et al.  Statistical thermodynamics of surfaces, interfaces, and membranes , 1995 .

[25]  Erwin Frey,et al.  Thermal fluctuations of grafted microtubules provide evidence of a length-dependent persistence length , 2005, Proceedings of the National Academy of Sciences.

[26]  Radial Distribution Function of Semiflexible Polymers. , 1996, Physical review letters.

[27]  J. Prost,et al.  Mechanism of actin-based motility: a dynamic state diagram. , 2005, Biophysical journal.

[28]  Julie A. Theriot,et al.  Loading history determines the velocity of actin-network growth , 2005, Nature Cell Biology.

[29]  R. Roth,et al.  Entropic torque. , 2002, Physical review letters.

[30]  G. Oster,et al.  Cell motility driven by actin polymerization. , 1996, Biophysical journal.

[31]  M. Abramowitz,et al.  Handbook of Mathematical Functions With Formulas, Graphs and Mathematical Tables (National Bureau of Standards Applied Mathematics Series No. 55) , 1965 .

[32]  Gary G. Borisy,et al.  Arp2/3 Complex and Actin Depolymerizing Factor/Cofilin in Dendritic Organization and Treadmilling of Actin Filament Array in Lamellipodia , 1999, The Journal of cell biology.

[33]  C. Kocks,et al.  Polarized distribution of Listeria monocytogenes surface protein ActA at the site of directional actin assembly. , 1993, Journal of cell science.

[34]  Transverse fluctuations of grafted polymers. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[35]  E. Hansen A Table of Series and Products , 1977 .

[36]  Julie A. Theriot,et al.  Actin microfilament dynamics in locomoting cells , 1991, Nature.

[37]  M. F.,et al.  Bibliography , 1985, Experimental Gerontology.

[38]  J. Small Lamellipodia architecture: actin filament turnover and the lateral flow of actin filaments during motility. , 1994, Seminars in cell biology.

[39]  F. Oosawa,et al.  A theory of linear and helical aggregations of macromolecules. , 1962, Journal of molecular biology.

[40]  G. Oster,et al.  The physics of lamellipodial protrusion , 1996, European Biophysics Journal.

[41]  P. Sansonetti,et al.  Entry of Shigella flexneri into HeLa cells: evidence for directed phagocytosis involving actin polymerization and myosin accumulation , 1987, Infection and immunity.

[42]  P. Cossart,et al.  Identification of two regions in the N‐terminal domain of ActA involved in the actin comet tail formation by Listeria monocytogenes , 1997, The EMBO journal.

[43]  M. S. Turner,et al.  The force generated by biological membranes on a polymer rod and its response: statics and dynamics. , 2004, The Journal of chemical physics.

[44]  Kurt I. Anderson,et al.  Contact dynamics during keratocyte motility , 2000, Current Biology.

[45]  E. Evans,et al.  Strength of a weak bond connecting flexible polymer chains. , 1999, Biophysical journal.

[46]  A. Wegner,et al.  Head to tail polymerization of actin. , 1976, Journal of molecular biology.

[47]  T. C. Lubensky Soft condensed matter physics , 1997 .

[48]  R. Lipowsky Stacks and bunches of fluid membranes , 1994 .

[49]  Erwin Frey,et al.  Tracer studies on f-actin fluctuations. , 2002, Physical review letters.

[50]  T. Mitchison,et al.  Actin-Based Cell Motility and Cell Locomotion , 1996, Cell.

[51]  T D Pollard,et al.  Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. , 2000, Annual review of biophysics and biomolecular structure.

[52]  Julie A. Theriot,et al.  Cooperative symmetry-breaking by actin polymerization in a model for cell motility , 1999, Nature Cell Biology.

[53]  Leah Edelstein-Keshet,et al.  Regulation of actin dynamics in rapidly moving cells: a quantitative analysis. , 2002, Biophysical journal.

[54]  D. Beysens,et al.  Dynamical Networks in Physics and Biology , 1998 .

[55]  A. Oudenaarden,et al.  Actin Polymerization: Forcing Flat Faces Forward , 2004, Current Biology.

[56]  Gary G. Borisy,et al.  Dendritic organization of actin comet tails , 2001, Current Biology.

[57]  C. Sykes,et al.  The actin slingshot. , 2005, Current opinion in cell biology.

[58]  James L. McGrath,et al.  Steps and fluctuations of Listeria monocytogenes during actin-based motility , 2000, Nature.

[59]  T D Pollard,et al.  Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments , 1986, The Journal of cell biology.

[60]  Bimodality in the transverse fluctuations of a grafted semiflexible polymer and the diffusion-convection analogue: an effective-medium approach. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[61]  M. Carlier,et al.  Control of Actin Dynamics in Cell Motility , 2022 .

[62]  K. Rottner,et al.  Actin polymerization machinery: the finish line of signaling networks, the starting point of cellular movement , 2005, Cellular and Molecular Life Sciences CMLS.

[63]  Entropic forces generated by grafted semiflexible polymers. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[64]  J. Kovac,et al.  Modified Gaussian model for rubber elasticity. 2. The wormlike chain , 1982 .

[65]  Gary G. Borisy,et al.  Analysis of the Actin–Myosin II System in Fish Epidermal Keratocytes: Mechanism of Cell Body Translocation , 1997, The Journal of cell biology.

[66]  R. Lipowsky,et al.  Binding and unbinding of lipid membranes: A Monte Carlo study. , 1989, Physical review letters.

[67]  Alexander van Oudenaarden,et al.  Probing polymerization forces by using actin-propelled lipid vesicles , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Marie-France Carlier,et al.  The dynamics of actin-based motility depend on surface parameters , 2002, Nature.

[69]  Jeffrey Kovac,et al.  Modified Gaussian Model for Rubber Elasticity , 1978 .

[70]  Marie-France Carlier,et al.  Mechanism of Actin-Based Motility , 2001, Science.

[71]  Marie-France Carlier,et al.  Forces generated during actin-based propulsion: a direct measurement by micromanipulation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[72]  R. Lipowsky Lines of Renormalization Group Fixed Points for Fluid and Crystalline Membranes , 1988 .

[73]  N. Boccara,et al.  Physics of Amphiphilic Layers , 1987 .

[74]  T. Pollard,et al.  Cellular Motility Driven by Assembly and Disassembly of Actin Filaments , 2003, Cell.

[75]  J. Hermans,et al.  The statistics of stiff chains, with applications to light scattering , 1952 .

[76]  P. Cossart,et al.  Actin-based motility of intracellular pathogens. , 2005, Current opinion in microbiology.

[77]  Julie A. Theriot,et al.  Principles of locomotion for simple-shaped cells , 1993, Nature.

[78]  Julie A. Theriot,et al.  The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization , 1992, Nature.

[79]  J. Kovac,et al.  Polymer conformational statistics. III. Modified Gaussian models of stiff chains , 1973 .

[80]  Julie A. Theriot,et al.  Secrets of actin-based motility revealed by a bacterial pathogen , 2000, Nature Reviews Molecular Cell Biology.

[81]  G. Ermentrout,et al.  Models for spatial polymerization dynamics of rod-like polymers , 2000, Journal of mathematical biology.

[82]  Marie-France Carlier,et al.  Reconstitution of actin-based motility of Listeria and Shigella using pure proteins , 1999, Nature.