Computational Model for Cell Migration in Three- Dimensional Matrices

¹ Whitehead Institute
² MIT

^* To whom correspondence should be addressed. E-mail: hamid{at}wi.mit.edu.

Submitted on February 4, 2005
Revised on April 25, 2005
Accepted on 16 May 2005

	Abstract

While computational models for cell migration on two- dimensional substrata [DiMilla et al., Biophysical Journal (1991)] have described how various molecular and cellular properties and physiochemical processes are integrated to accomplish cell locomotion, the same issues, along with certain new ones, might contribute differently to a model for migration within three-dimensional matrices. To address this more complicated situation, we have developed a computational model for cell migration in three-dimensional matrices using a force-based dynamics approach. This model determines an overall locomotion velocity vector, comprising speed and direction, for individual cells based on internally-generated forces transmitted into external traction forces and considering a time-scale during which multiple attachment and detachment events are integrated. Key parameters characterize cell and matrix properties, including cell/matrix adhesion and mechanical and steric properties of the matrix; critical underlying molecular properties are incorporated explicitly or implicitly. Model predictions agree well with experimental results for the limiting case of migration on two-dimensional substrata as well as recent experiments in three-dimensional natural tissues and synthetic gels. Certain predicted features such as biphasic behavior of speed with density of matrix ligands for three-dimensional migration are qualitatively similar to their two-dimensional counterparts, but new effects generally absent in two-dimensional systems such as effects due to matrix sterics and mechanics are now predicted to arise in many three-dimensional situations. As one particular example manifestation of these effects, the optimal levels of cell receptor expression and matrix ligand density yielding maximal migration are dependent on matrix mechanical compliance.

Key Words: adhesion, cell migration, extra cellular matrix, force generation

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