A computational model of bleb formation.

Blebbing occurs when the cytoskeleton detaches from the cell membrane, resulting in the pressure-driven flow of cytosol towards the area of detachment and the local expansion of the cell membrane. Recent interest has focused on cells that use blebbing for migrating through 3D fibrous matrices. In particular, metastatic cancer cells have been shown to use blebs for motility. A dynamic computational model of the cell is presented that includes mechanics of and the interactions between the intracellular fluid, the actin cortex and the cell membrane. The computational model is used to explore the relative roles in bleb formation time of cytoplasmic viscosity and drag between the cortex and the cytosol. A regime of values for the drag coefficient and cytoplasmic viscosity values that match bleb formation timescales is presented. The model results are then used to predict the Darcy permeability and the volume fraction of the cortex.

[1]  Charles S. Peskin,et al.  2-D Parachute Simulation by the Immersed Boundary Method , 2006, SIAM J. Sci. Comput..

[2]  L. Mahadevan,et al.  Non-equilibration of hydrostatic pressure in blebbing cells , 2005, Nature.

[3]  L Mahadevan,et al.  Life and times of a cellular bleb. , 2008, Biophysical journal.

[4]  A. Mastro,et al.  Diffusion of a small molecule in the cytoplasm of mammalian cells. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Chatterjee,et al.  Nonuniform fiber networks and fiber-based composites: Pore size distributions and elastic moduli , 2010 .

[6]  J. Trinkaus,et al.  Microvilli and blebs as sources of reserve surface membrane during cell spreading. , 1976, Experimental cell research.

[7]  J. Tinevez,et al.  Role of cortical tension in bleb growth , 2009, Proceedings of the National Academy of Sciences.

[8]  J. Stockie Modelling and simulation of porous immersed boundaries , 2009 .

[9]  J. Davies,et al.  Molecular Biology of the Cell , 1983, Bristol Medico-Chirurgical Journal.

[10]  Daniel Isabey,et al.  Assessment of mechanical properties of adherent living cells by bead micromanipulation: comparison of magnetic twisting cytometry vs optical tweezers. , 2002, Journal of biomechanical engineering.

[11]  Peter Friedl,et al.  Compensation mechanism in tumor cell migration , 2003, The Journal of cell biology.

[12]  Julie A. Theriot,et al.  Intracellular fluid flow in rapidly moving cells , 2009, Nature Cell Biology.

[13]  Jason C. Mills,et al.  Apoptotic Membrane Blebbing Is Regulated by Myosin Light Chain Phosphorylation , 1998, The Journal of cell biology.

[14]  Timothy J. Mitchison,et al.  Reassembly of contractile actin cortex in cell blebs , 2006, The Journal of cell biology.

[15]  Denis Wirtz,et al.  Particle-tracking microrheology of living cells: principles and applications. , 2009, Annual review of biophysics.

[16]  M. Sheetz,et al.  Continuous membrane-cytoskeleton adhesion requires continuous accommodation to lipid and cytoskeleton dynamics. , 2006, Annual review of biophysics and biomolecular structure.

[17]  O. Fackler,et al.  Cell motility through plasma membrane blebbing , 2008, The Journal of cell biology.

[18]  B. Geiger,et al.  Mobility of microinjected rhodamine actin within living chicken gizzard cells determined by fluorescence photobleaching recovery , 1982, Cell.

[19]  J. Bear Dynamics of Fluids in Porous Media , 1975 .

[20]  Guillaume Charras,et al.  Blebs lead the way: how to migrate without lamellipodia , 2008, Nature Reviews Molecular Cell Biology.

[21]  C. Peskin Numerical analysis of blood flow in the heart , 1977 .

[22]  D. F. James,et al.  The permeability of fibrous porous media , 1986 .

[23]  Simon L. Goren,et al.  Model for predicting pressure drop and filtration efficiency in fibrous media , 1968 .

[24]  Sorin Mitran,et al.  A numerical model of cellular blebbing: a volume-conserving, fluid-structure interaction model of the entire cell. , 2010, Journal of biomechanics.

[25]  Y. Wang,et al.  Microinjection of the catalytic fragment of myosin light chain kinase into dividing cells: effects on mitosis and cytokinesis , 1991, The Journal of cell biology.