Abstract
Actin polymerization drives cell membrane protrusions and the propulsion of intracellular pathogens. The molecular mechanisms driving actin polymerization are not yet fully understood. Various mathematical models have been proposed to explain how cells convert chemical energy released upon actin polymerization into a pushing force on a surface. These models have attempted to explain puzzling properties of actin-based motility, including persistent attachment of the network to the membrane during propulsion and the interesting trajectories of propelled particles. These models fall generally into two classes: those requiring filament (+)-ends to fluctuate freely from the membrane to add subunits, and those where filaments elongate with their (+)-ends persistently associated with surface through filament end-tracking proteins (“actoclampin” models). This review compares and contrasts the key predictions of these two classes of models with regard to force–velocity profiles, and evaluates them with respect to experiments with biomimetic particles, and the experimental evidence on the role of end-tracking proteins such as formins and nucleation-promoting factors in actin-based motility.
Similar content being viewed by others
References
Bray D.: Cell Movements: from Molecules to Motility. 2nd edn. Garland Publishing, New York (2001)
Stevens J.M., Galyov E.E., Stevens M.P.: Actin-dependent movement of bacterial pathogens. Nat. Rev. Microbiol. 4, 91–101 (2006)
Kuo S.C., McGrath J.L.: Steps and fluctuations of Listeria monocytogenes during actin-based motility. Nature 407, 1026–1029 (2000)
McGrath J.L., Eungdamrong N.J., Fisher C.I., Peng F., Mahadevan L., Mitchison T.J., Kuo S.C.: The force–velocity relationship for the actin-based motility of Listeria monocytogenes. Curr. Biol. 13, 329–332 (2003)
Giardini P.A., Fletcher D.A., Theriot J.A.: Compression forces generated by actin comet tails on lipid vesicles. Proc. Natl. Acad. Sci. USA 100, 6493–6498 (2003)
Upadhyaya A., Chabot J.R., Andreeva A., Samadani A., Oudenaarden A.: Probing polymerization forces by using actin-propelled lipid vesicles. Proc. Natl. Acad. Sci. USA 100, 4521–4526 (2003)
Boukellal H., Campas O., Joanny J.F., Prost J., Sykes C.: Soft Listeria: actin-based propulsion of liquid drops. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 69, 061906 (2004)
Zeile W.L., Zhang F., Dickinson R.B., Purich D.L.: Listeria’s right-handed helical rocket-tail trajectories: mechanistic implications for force generation in actin-based motility. Cell Motil. Cytoskelet. 60, 121–128 (2005)
Robbins J.R., Theriot J.A.: Listeria monocytogenes rotates around its long axis during actin-based motility. Curr. Biol. 13, R754–756 (2003)
Bernheim-Groswasser A., Wiesner S., Golsteyn R.M., Carlier M.F., Sykes C.: The dynamics of actin-based motility depend on surface parameters. Nature 417, 308–311 (2002)
Bernheim-Groswasser A., Prost J., Sykes C.: Mechanism of actin-based motility: a dynamic state diagram. Biophys. J. 89, 1411–1419 (2005)
Pollard T.D., Borisy G.G: Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003)
Ponti A., Machacek M., Gupton S.L., Waterman-Storer C.M., Danuser G.: Two distinct actin networks drive the protrusion of migrating cells. Science 305, 1782–1786 (2004)
Bugyi, B., Le Clainche, C., Romet-Lemonne, G., Carlier, M.F.: How do in vitro reconstituted actin-based motility assays provide insight into in vivo behavior? FEBS Lett. (2008)
Pollard T.D., Blanchoin L., Mullins R.D.: Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu. Rev. Biophys. Biomol. Struct. 29, 545–576 (2000)
Hill T.L.: Microfilament or microtubule assembly or disassembly against a force. Proc. Natl. Acad. Sci. USA 78, 5613–5617 (1981)
Cooper J.A.: The role of actin polymerization in cell motility. Annu. Rev. Physiol. 53, 585–605 (1991)
Carlier M.F., Laurent V., Santolini J., Melki R., Didry D., Xia G.X., Hong Y., Chua N.H., Pantaloni D.: Actin depolymerizing factor (ADF/cofilin) enhances the rate of filament turnover: implication in actin-based motility. J. Cell Biol. 136, 1307–1322 (1997)
Mogilner A., Oster G.: Cell motility driven by actin polymerization. Biophys. J. 71, 3030–3045 (1996)
Mogilner A., Edelstein-Keshet L.: Regulation of actin dynamics in rapidly moving cells: a quantitative analysis. Biophys. J. 83, 1237–1258 (2002)
Mogilner A., Oster G.: Polymer motors: pushing out the front and pulling up the back. Curr. Biol. 13, R721–733 (2003)
Noireaux V., Golsteyn R.M., Friederich E., Prost J., Antony C., Louvard D., Sykes C.: Growing an actin gel on spherical surfaces. Biophys. J. 78, 1643–1654 (2000)
Abraham V.C., Krishnamurthi V., Taylor D.L., Lanni F.: The actin-based nanomachine at the leading edge of migrating cells. Biophys. J. 77, 1721–1732 (1999)
Pring M., Weber A., Bubb M.R.: Profilin-actin complexes directly elongate actin filaments at the barbed end. Biochemistry 31, 1827–1836 (1992)
Romero S., Didry D., Larquet E., Boisset N., Pantaloni D., Carlier M.F.: How ATP hydrolysis controls filament assembly from profilin-actin: implication for formin processivity. J. Biol. Chem. 282, 8435–8445 (2007)
Carlier M.F., Jean C., Rieger K.J., Lenfant M., Pantaloni D.: Modulation of the interaction between G-actin and thymosin beta 4 by the ATP/ADP ratio: possible implication in the regulation of actin dynamics. Proc. Natl. Acad. Sci. USA 90, 5034–5038 (1993)
Kinosian H.J., Selden L.A., Gershman L.C., Estes J.E.: Actin filament barbed end elongation with nonmuscle MgATP-actin and MgADP-actin in the presence of profilin. Biochemistry 41, 6734–6743 (2002)
Yarmola E.G., Bubb M.R.: Profilin: emerging concepts and lingering misconceptions. Trends Biochem. Sci. 31, 197–205 (2006)
Kang F., Purich D.L., Southwick F.S.: Profilin promotes barbed-end actin filament assembly without lowering the critical concentration. J. Biol. Chem. 274, 36963–36972 (1999)
Howard J.: Mechanics of Motor Proteins and the Cytoskeleton. Sinauer, Sunderland (2001)
Dickinson R.B., Caro L., Purich D.L.: Force generation by cytoskeletal filament end-tracking proteins. Biophys. J. 87, 2838–2854 (2004)
Kinosian H.J., Selden L.A., Gershman L.C., Estes J.E.: Interdependence of profilin, cation, and nucleotide binding to vertebrate non-muscle actin. Biochemistry 39, 13176–13188 (2000)
Peskin C.S., Odell G.M., Oster G.F.: Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys. J. 65, 316–324 (1993)
Mogilner A., Oster G.: Force Generation by Actin Polymerization II: The Elastic Ratchet and Tethered Filaments. Biophys. J. 84, 1591–1605 (2003)
Gerbal F., Laurent V., Ott A., Carlier M.F., Chaikin P., Prost J.: Measurement of the elasticity of the actin tail of Listeria monocytogenes. Eur. Biophys. J. 29, 134–140 (2000)
Bell G.I.: Models for the specific adhesion of cells to cells. Science 200, 618–627 (1978)
Trichet L., Campas O., Sykes C., Plastino J.: VASP governs actin dynamics by modulating filament anchoring. Biophys. J. 92, 1081–1089 (2007)
Gerbal F., Chaikin P., Rabin Y., Prost J.: An elastic analysis of Listeria monocytogenes propulsion. Biophys. J. 79, 2259–2275 (2000)
Soo F.S., Theriot J.A.: Adhesion controls bacterial actin polymerization-based movement. Proc. Natl. Acad. Sci. USA 102, 16233–16238 (2005)
Parekh S.H., Chaudhuri O., Theriot J.A., Fletcher D.A.: Loading history determines the velocity of actin-network growth. Nat. Cell Biol. 7, 1119–1123 (2005)
Prass M., Jacobson K., Mogilner A., Radmacher M.: Direct measurement of the lamellipodial protrusive force in a migrating cell. J. Cell Biol. 174, 767–772 (2006)
Marcy Y., Prost J., Carlier M.F., Sykes C.: Forces generated during actin-based propulsion: a direct measurement by micromanipulation. Proc. Natl. Acad. Sci. USA 101, 5992–5997 (2004)
Dickinson R.B., Purich D.L.: Diffusion rate limitations in actin-based propulsion of hard and deformable particles. Biophys. J. 91, 1548–1563 (2006)
Carlsson A.E.: Growth velocities of branched actin networks. Biophys. J. 84, 2907–2918 (2003)
Wiesner S., Helfer E., Didry D., Ducouret G., Lafuma F., Carlier M.F., Pantaloni D.: A biomimetic motility assay provides insight into the mechanism of actin-based motility. J. Cell Biol. 160, 387–398 (2003)
Paluch E., Gucht J., Joanny J.F., Sykes C.: Deformations in actin comets from rocketing beads. Biophys. J. 91, 3113–3122 (2006)
Brieher W.M., Coughlin M., Mitchison T.J.: Fascin-mediated propulsion of Listeria monocytogenes independent of frequent nucleation by the Arp2/3 complex. J. Cell Biol. 165, 233–242 (2004)
Co C., Wong D.T., Gierke S., Chang V., Taunton J.: Mechanism of actin network attachment to moving membranes: barbed end capture by N-WASP WH2 domains. Cell 128, 901–913 (2007)
Gholami A., Falke M., Frey E.: Velocity oscillations in actin-based motility. New J. Phys. 10, 1–12 (2008)
Delatour V., Helfer E., Didry D., Le K.H., Gaucher J.F., Carlier M.F., Romet-Lemonne G.: Arp2/3 controls the motile behavior of N-WASP-functionalized GUVs and modulates N-WASP surface distribution by mediating transient links with actin filaments. Biophys. J. 94, 4890–4905 (2008)
Dickinson R.B., Purich D.L.: Clamped-filament elongation model for actin-based motors. Biophys. J. 82, 605–617 (2002)
Chereau, D., Dominguez, R.: Understanding the role of the G-actin-binding domain of Ena/VASP in actin assembly. J. Struct. Biol. (2006)
Romero S., Le Clainche C., Didry D., Egile C., Pantaloni D., Carlier M.F.: Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 119, 419–429 (2004)
Vavylonis D., Kovar D.R., O’Shaughnessy B., Pollard T.D.: Model of formin-associated actin filament elongation. Mol. Cell 21, 455–466 (2006)
Paul A., Pollard T.: The role of the FH1 domain and profilin in formin-mediated actin-filament elongation and nucleation. Curr. Biol. 18, 9–19 (2008)
Wei J., Leyh T.S.: Isomerization couples chemistry in the ATP sulfurylase-GTPase system. Biochemistry 38, 6311–6316 (1999)
Eisenberg E., Hill T.L.: Muscle contraction and free energy transduction in biological systems. Science 227, 999–1006 (1985)
Chereau D., Kerff F., Graceffa P., Grabarek Z., Langsetmo K., Dominguez R.: Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly. Proc. Natl. Acad. Sci. USA 102, 16644–16649 (2005)
Zalevsky J., Lempert L., Kranitz H., Mullins R.D.: Different WASP family proteins stimulate different Arp2/3 complex-dependent actin-nucleating activities. Curr. Biol. 11, 1903–1913 (2001)
Stevens M.P., Stevens J.M., Jeng R.L., Taylor L.A., Wood M.W., Hawes P., Monaghan P., Welch M.D., Galyov E.E.: Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Mol. Microbiol. 56, 40–53 (2005)
Gouin E., Egile C., Dehoux P., Villiers V., Adams J., Gertler F., Li R., Cossart P.: The RickA protein of Rickettsia conorii activates the Arp2/3 complex. Nature 427, 457–461 (2004)
Mattila P.K., Salminen M., Yamashiro T., Lappalainen P.: Mouse MIM, a tissue-specific regulator of cytoskeletal dynamics, interacts with ATP-actin monomers through its C-terminal WH2 domain. J. Biol. Chem. 278, 8452–8459 (2003)
Hertzog M., Yarmola E.G., Didry D., Bubb M.R., Carlier M.F.: Control of actin dynamics by proteins made of beta-thymosin repeats: the actobindin family. J. Biol. Chem. 277, 14786–14792 (2002)
Zhu J., Carlsson A.E.: Growth of attached actin filaments. Eur. Phys. J. E. Soft Matter 21, 209–222 (2006)
Kovar D.R., Harris E.S., Mahaffy R., Higgs H.N., Pollard T.D.: Control of the assembly of ATP- and ADP-actin by formins and profilin. Cell 124, 423–435 (2006)
Barzik M., Kotova T.I., Higgs H.N., Hazelwood L., Hanein D., Gertler F.B., Schafer D.A.: Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins. J. Biol. Chem. 280, 28653–28662 (2005)
Kang F., Laine R.O., Bubb M.R., Southwick F.S., Purich D.L.: Profilin interacts with the Gly-Pro-Pro-Pro-Pro-Pro sequences of vasodilator-stimulated phosphoprotein (VASP): implications for actin-based Listeria motility. Biochemistry 36, 8384–8392 (1997)
Grenklo S., Geese M., Lindberg U., Wehland J., Karlsson R., Sechi A.S.: A crucial role for profilin-actin in the intracellular motility of Listeria monocytogenes. EMBO Rep. 4, 523–529 (2003)
Dickinson R.B., Southwick F.S., Purich D.L.: A direct-transfer polymerization model explains how the multiple profilin-binding sites in the actoclampin motor promote rapid actin-based motility. Arch. Biochem. Biophys. 406, 296–301 (2002)
Haffner C., Jarchau T., Reinhard M., Hoppe J., Lohmann S.M., Walter U.: Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament-associated protein VASP. Embo J. 14, 19–27 (1995)
Rivero-Lezcano O.M., Marcilla A., Sameshima J.H., Robbins K.C.: Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. Mol. Cell Biol. 15, 5725–5731 (1995)
She H.Y., Rockow S., Tang J., Nishimura R., Skolnik E.Y., Chen M., Margolis B., Li W.: Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells. Mol. Biol. Cell 8, 1709–1721 (1997)
Wu Y., Spencer S.D., Lasky L.A.: Tyrosine phosphorylation regulates the SH3-mediated binding of the Wiskott-Aldrich syndrome protein to PSTPIP, a cytoskeletal-associated protein. J. Biol. Chem. 273, 5765–5770 (1998)
Oda A., Ochs H.D., Lasky L.A., Spencer S., Ozaki K., Fujihara M., Handa M., Ikebuchi K., Ikeda H.: CrkL is an adapter for Wiskott–Aldrich syndrome protein and Syk. Blood 97, 2633–2639 (2001)
Rohatgi R., Nollau P., Ho H.Y., Kirschner M.W., Mayer B.J.: Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway. J. Biol. Chem. 276, 26448–26452 (2001)
Rivera G.M., Briceno C.A., Takeshima F., Snapper S.B., Mayer B.J.: Inducible clustering of membrane-targeted SH3 domains of the adaptor protein Nck triggers localized actin polymerization. Curr. Biol. 14, 11–22 (2004)
Plastino J., Lelidis I., Prost J., Sykes C.: The effect of diffusion, depolymerization and nucleation promoting factors on actin gel growth. Eur. Biophys. J. 33, 310–320 (2004)
Soo F.S., Theriot J.A.: Large-scale quantitative analysis of sources of variation in the actin polymerization-based movement of Listeria monocytogenes. Biophys. J. 89, 703–723 (2005)
Shaevitz J.W., Fletcher D.A.: Load fluctuations drive actin network growth. Proc. Natl. Acad. Sci. USA 104, 15688–15692 (2007)
Plastino J., Olivier S., Sykes C.: Actin filaments align into hollow comets for rapid VASP-mediated propulsion. Curr. Biol. 14, 1766–1771 (2004)
Zigmond S.H., Evangelista M., Boone C., Yang C., Dar A.C., Sicheri F., Forkey J., Pring M.: Formin leaky cap allows elongation in the presence of tight capping proteins. Curr. Biol. 13, 1820–1823 (2003)
Higashida C., Miyoshi T., Fujita A., Oceguera-Yanez F., Monypenny J., Andou Y., Narumiya S., Watanabe N.: Actin polymerization-driven molecular movement of mDia1 in living cells. Science 303, 2007–2010 (2004)
Kovar D.R., Pollard T.D.: Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. Proc. Natl. Acad. Sci. USA 101, 14725–14730 (2004)
Footer M.J., Kerssemakers J.W., Theriot J.A., Dogterom M.: Direct measurement of force generation by actin filament polymerization using an optical trap. Proc. Natl. Acad. Sci. USA 104, 2181–2186 (2007)
Kozlov M.M., Bershadsky A.D.: Processive capping by formin suggests a force-driven mechanism of actin polymerization. J. Cell Biol. 167, 1011–1017 (2004)
Cameron L.A., Svitkina T.M., Vignjevic D., Theriot J.A., Borisy G.G.: Dendritic organization of actin comet tails. Curr. Biol. 11, 130–135 (2001)
Samarin S., Romero S., Kocks C., Didry D., Pantaloni D., Carlier M.F.: How VASP enhances actin-based motility. J. Cell Biol. 163, 131–142 (2003)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dickinson, R.B. Models for actin polymerization motors. J. Math. Biol. 58, 81–103 (2009). https://doi.org/10.1007/s00285-008-0200-4
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00285-008-0200-4
Keywords
- Actin-based motility
- Filament end-tracking motor
- Brownian ratchet
- Listeria
- Wiskott–Aldrich syndrome protein
- Vasodilator-stimulated phosphoprotein
- Arp2/3 complex