Complex Matrix Remodeling and Durotaxis Can Emerge From Simple Rules for Cell-Matrix Interaction in Agent-Based Models

Using a top-down approach, an agent-based model was developed within Netlogo where cells and extracellular matrix (ECM) fibers were composed of multiple agents to create deformable structures capable of exerting, reacting to and transmitting mechanical forces. Simulated cells remodeled the fibrous matrix to change both the density and alignment of the fibers and migrated within the matrix in ways that are consistent with previous experimental work. Cells compacted the matrix in their pericellular regions much more than the average compaction experienced for the entire matrix. Between pairs of cells, the anisotropy index increased, fibers became more aligned in the direction parallel to a line connecting the two cells and the matrix density increased. To explore the potential contribution of matrix stiffness gradients in the observed migration (i.e., durotaxis), a single-cell on a regular lattice of fibers possessing a stiffness gradient was simulated. Cells migrated preferentially in the direction of increasing stiffness at a rate of ∼2 cell diameter per 10,000 AU. This work demonstrates that matrix remodeling and durotaxis, both complex phenomena, might be emergent behaviors based on just a few rules that control how a cell can interact with a fibrous ECM.