Computational model for migration of a cell cluster in three-dimensional matrices

Abstract

This paper presents a first forced-based dynamics computer model of a cell cluster moving collectively in a 3D environment mimicking the extracellular matrix. In general, collective cell migration is a relevant part of the mechanisms for tissue repair, morphogenesis, and cancer invasion. Particularly in cancer, invasion occurs through multicellular 3D strands as well as collective cell clusters. Because cancer is a slow process, these clusters have not been carefully observed. However, the prevalence of this mechanism of cell locomotion makes it a target for study. Due to the different molecular mechanisms involved in this movement and the complex relations among them, a computer model would be of great use. The model presented here takes into account ligand concentration, matrix metalloproteinase activity, and cluster geometry based on experimental findings and experimentally validated single cell computer models; thus incorporating implicitly different underlying molecular properties. The velocity profiles of the cell clusters were recorded and analyzed. In particular seven different profiles are observed based on different participation of ligands, proteinases, and mechanical forces involved. The model is successful in showing potential effects of altering single variables in a system of cells in motion. Special emphasis is made on future directions for improvement and the variables to be potentially modulated to simulate particular physiological conditions. © 2011 Biomedical Engineering Society.