The actin filamant system of eukaryotic cells is the dynamical structure primarily responsible for the so called """"""""amoeboid"""""""" motions: phagocytosis, cytokinesis, pseudopodal extension/retraction, cytoplasmic streaming, cell spreading and crawling locomotion on surfaces. The advent of supercomputers and the associated technology for numerically solving systems of nonlinear partial differential equations makes it possible to investigate the properties of realistic continuum mechanical models of the actin filament system. This means that, for the first time, the detailed comparison of theories of cell motion with the results of observation and experiment can be carried through. The potential impact of continuum mechanics and supercomputers on biological understanding of the cytoskeleton and amoeboid motility can be gauged by reference to the revolutionary changes currently underway in the area of macro-molecular structure and function. To realize these potentialities, however, existing theoretical work must be greatly extended. In the past, computational methods for solving models of the cytoplasmic mechanics have been restricted to the confined motions of isotropic contractile networks (i.e., motions within a fixed spatial domain in which the actin filaments are randomly orientated). As a results, these methods could not be applied to many of the most interesting forms of cell motility (e.g., pseudopodal extension). It is now proposed to improve existing continuum models and associated numerical techniques so as to remove these limitations. We propose to demonstrate the practical utility of our theoretical and computational methodologies by carrying out detailed mechanical analyses of experimental systems for which good data are available. The first such analysis will be of the problem of the stability and self assembly of the monopodial form and the connected problem of pseudopodial extension in the giant free living amoebae such as A. proteus. Subsequently, we propose to analyze the dynamics of the leading lamella of tissue culture cells such as fibroblasts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021002-06
Application #
3130892
Study Section
Special Emphasis Panel (SSS (B))
Project Start
1984-09-01
Project End
1994-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Los Alamos National Lab
Department
Type
Organized Research Units
DUNS #
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
Drury, J L; Dembo, M (1999) Hydrodynamics of micropipette aspiration. Biophys J 76:110-28
Dembo, M; Wang, Y L (1999) Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys J 76:2307-16
Oliver, T; Jacobson, K; Dembo, M (1998) Design and use of substrata to measure traction forces exerted by cultured cells. Methods Enzymol 298:497-521
He, X; Dembo, M (1997) On the mechanics of the first cleavage division of the sea urchin egg. Exp Cell Res 233:252-73
Dembo, M; Oliver, T; Ishihara, A et al. (1996) Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys J 70:2008-22
He, X; Dembo, M (1996) Numerical simulation of oil-droplet cleavage by surfactant. J Biomech Eng 118:201-9
Goldstein, B; Dembo, M (1995) Approximating the effects of diffusion on reversible reactions at the cell surface: ligand-receptor kinetics. Biophys J 68:1222-30
He, X; Dembo, M (1995) Modeling chemoattractant-elicited relocalization of myosin filaments in Dictyostelium. Biochem Cell Biol 73:421-9
Oliver, T; Dembo, M; Jacobson, K (1995) Traction forces in locomoting cells. Cell Motil Cytoskeleton 31:225-40
Ward, M D; Dembo, M; Hammer, D A (1995) Kinetics of cell detachment: effect of ligand density. Ann Biomed Eng 23:322-31

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