Using 3D Discrete Fiber Models to Investigate Cell-Mediated Extracellular Matrix Remodeling*

Motile cells within a fibrous matrix not only move but also rearrange the matrix around them, with potential consequences for the local and global tissue structure. Because cells also sense and respond to changes in the matrix, this rearrangement provides a mechanism for cell-cell communication. We present a coarse-grained computational model of collagen matrix rearrangement by one or more cells, focusing on the changes in the matrix and comparing the results to experimental observation. The model represents collagen fibers as strings of beads that intersect at some beads to form a large network; an important feature of the beads is that they can bond to beads from nearby fiber segments, leading to irreversible rearrangement of the fibers. The action of cellular pseudopodia is represented by a collection of "tractors," which extend from the cell, bind to the surrounding matrix, and then retract, pulling the matrix with them. The combined effect of the tractors and the interfibrillar bonding is a large-scale rearrangement and, in the case of multiple cells, local realignment of the surrounding fiber network.