Skip to main content
Log in

Coarse-grained Brownian ratchet model of membrane protrusion on cellular scale

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Membrane protrusion is a mechanochemical process of active membrane deformation driven by actin polymerization. Previously, Brownian ratchet (BR) was modeled on the basis of the underlying molecular mechanism. However, because the BR requires a priori load that cannot be determined without information of the cell shape, it cannot be effective in studies in which resultant shapes are to be solved. Other cellular-scale models describing the protrusion have also been suggested for modeling a whole cell; however, these models were not developed on the basis of coarse-grained physics representing the underlying molecular mechanism. Therefore, to express the membrane protrusion on the cellular scale, we propose a novel mathematical model, the coarse-grained BR (CBR), which is derived on the basis of nonequilibrium thermodynamics theory. The CBR can reproduce the BR within the limit of the quasistatic process of membrane protrusion and can estimate the protrusion velocity consistently with an effective elastic constant that represents the state of the energy of the membrane. Finally, to demonstrate the applicability of the CBR, we attempt to perform a cellular-scale simulation of migrating keratocyte in which the proposed CBR is used for the membrane protrusion model on the cellular scale. The results show that the experimentally observed shapes of the leading edge are well reproduced by the simulation. In addition, The trend of dependences of the protrusion velocity on the curvature of the leading edge, the temperature, and the substrate stiffness also agreed with the other experimental results. Thus, the CBR can be considered an appropriate cellular-scale model to express the membrane protrusion on the basis of its underlying molecular mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abraham VC, Krishnamurthi V, Taylor DL, Lanni F (1999) The actin-based nanomachine at the leading edge of migrating cells. Biophys J 77: 1721–1732

    Article  Google Scholar 

  • Adachi T, Okeyo KO, Shitagawa Y, Hojo M (2009) Strain field in actin filament network in lamellipodia of migrating cells: implication for network reorganization. J Biomech 42: 297–302

    Article  Google Scholar 

  • Atilgan E, Wirtz D, Sun SX (2006) Mechanics and dynamics of actin-driven thin membrane protrusions. Biophy J 90: 65–76

    Article  Google Scholar 

  • Borisy GG, Svitkina TM (2000) Actin machinery: pushing the envelope. Curr Opin Cell Biol 12: 104–112

    Article  Google Scholar 

  • DeMali KA, Barlow CA, Burridge K (2002) Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J Cell Biol 159: 881–891

    Article  Google Scholar 

  • Dickinson RB, Purich DL (2002) Clamped-filament elongation model for actin-based motors. Biophy J 82: 605–617

    Article  Google Scholar 

  • Erdmann T, Schwarz US (2004) Stability of adhesion clusters under constant force. Phys Rev Lett 92: 108101–108102

    Article  Google Scholar 

  • Grimm HP, Verkhovsky AB, Mogilner A, Meister JJ (2003) Analysis of actin dynamics at the leading edge of crawling cells: implications for the shape of keratocyte lamellipodia. Eur Biophys J 32: 563–577

    Article  Google Scholar 

  • Henriksen JR, Ipsen JH (2004) Measurement of membrane elasticity by micro-pipette aspiration. Eur Phys J E 14: 149–167

    Article  Google Scholar 

  • Jarzynski C (1997) Nonequilibrium equality for free energy differences. Phys Rev Lett 78: 2690–2693

    Article  Google Scholar 

  • Keren K, Pincus Z, Allen GM, Barnhart EL, Marriott G, Mogilner A, Theriot JA (2008) Mechanism of shape determination in motile cells. Nature 453: 475–480

    Article  Google Scholar 

  • Lacayo CI, Pincus Z, VanDuijn MM, Wilson CA, Fletcher DA, Gertler FB, Mogilner A, Theriot JA (2007) Emergence of large-scale cell morphology and movement from local actin filament growth dynamics. PLoS Biol 5: 2035–2052

    Article  Google Scholar 

  • Lauffenburger DA, Horwitz AF (1996) Cell migration: a physically integrated molecular process. Cell 84: 359–369

    Article  Google Scholar 

  • Lee J, Ishihara A, Theriot JA, Jacobson K (1993) Principles of locomotion for simple-shaped cells. Nature 362: 167–171

    Article  Google Scholar 

  • Lo CM, Wang HB, Dembo M, Wang YL (2000) Cell movement is guided by the rigidity of the substrate. Biophys J 79: 144–152

    Article  Google Scholar 

  • Marée AFM, Jilkine A, Dawes A, Grieneisen VA, Edelstein-Keshet L (2006) Polarization and movement of keratocytes: a multiscale modelling approach. Bull Math Biol 68: 1169–1211

    Article  Google Scholar 

  • Méléard P, Gerbeaud C, Bardusco P, Jeandaine N, Mitov MD, Fernandez-Puente L (1998) Mechanical properties of model membranes studied from shape transformations of giant vesicles. Biochimie 80: 401–413

    Article  Google Scholar 

  • Mogilner A, Oster G (1996) Cell motility driven by actin polymerization. Biophys J 71: 3030–3045

    Article  Google Scholar 

  • Mogilner A, Oster G (2003) Force generation by actin polymerization II: the elastic ratchet and tethered filaments. Biophys J 84: 1591–1605

    Article  Google Scholar 

  • Mogilner A, Edelstein-Keshet L (2002) Regulation of actin dynamics in rapidly moving cells: a quantitative analysis. Biophys J 83: 1237–1258

    Article  Google Scholar 

  • Mogilner A, Rubinstein B (2005) The physics of filopodial protrusion. Biophys J 89: 782–795

    Article  Google Scholar 

  • Paul R, Heil P, Spatz JP, Schwarz US (2008) Propagation of mechanical stress through the actin cytoskeleton toward focal adhesions: model and experiment. Biophys J 94: 1470–1482

    Article  Google Scholar 

  • Pelham RJ Jr, Wang YL (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci U S A 94: 13661–13665

    Article  Google Scholar 

  • Peskin CS, Odell GM, Oster GF (1993) Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys J 65: 316–324

    Article  Google Scholar 

  • Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112: 453–465

    Article  Google Scholar 

  • Ponti A, Machacek M, Gupton SL, Waterman-Storer CM, Danuser G (2004) Two distinct actin networks drive the protrusion of migrating cells. Science 305: 1782–1786

    Article  Google Scholar 

  • Ream RA, Theriot JA, Somero GN (2003) Influences of thermal acclimation and acute temperature change on the motility of epithelial wound-healing cells (keratocytes) of tropical, temperate and Antarctic fish. J Exp Biol 206: 4539–4551

    Article  Google Scholar 

  • Rubinstein B, Jacobson K, Mogilner A (2005) Multiscale two- dimensional modeling of a motile simple-shaped cell. Multiscale Model Simul 3: 413–439

    Article  MATH  MathSciNet  Google Scholar 

  • Satyanarayana SVM, Baumgaertner A (2004) Shape and motility of a model cell: a computational study. J Chem Physics 121: 4255–4265

    Article  Google Scholar 

  • Seifert U (1997) Configurations of fluid membranes and vesicles. Adv Phys 46: 13–137

    Article  Google Scholar 

  • Sheetz MP, Sable JE, Döbereiner HG (2006) Continuous membrane-cytoskeleton adhesion requires continuous accommodation to lipid and cytoskeleton dynamics. Ann Rev Biophys Biomol Struct 35: 417–434

    Article  Google Scholar 

  • Small JV, Herzog M, Anderson K (1995) Actin filament organization in the fish keratocyte lamellipodium. J Cell Biol 129: 1275–1286

    Article  Google Scholar 

  • Theriot JA, Mitchison TJ (1991) Actin microfilament dynamics in locomoting cells. Nature 352: 126–131

    Article  Google Scholar 

  • Verkhovsky AB, Svitkina TM, Borisy GG (1999) Self-polarization and directional motility of cytoplasm. Curr Biol 9: 11–20

    Article  Google Scholar 

  • Yam PT, Wilson CA, Ji L, Hebert B, Barnhart EL, Dye NA, Wiseman PW, Danuser G, Theriot JA (2007) Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J Cell Biol 178: 1207–1221

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yasuhiro Inoue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Inoue, Y., Adachi, T. Coarse-grained Brownian ratchet model of membrane protrusion on cellular scale. Biomech Model Mechanobiol 10, 495–503 (2011). https://doi.org/10.1007/s10237-010-0250-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-010-0250-6

Keywords

Navigation