MULTISCALE AGENT-BASED SIMULATION FOR CHONDROGENIC PATTERN FORMATION IN VITRO

Abstract

Mathematical and computational multiscale models are becoming increasingly important investigative tools in developmental biological research. During certain developmental processes cells that start out as independent entities interact to form multicellular structures. Cells of the embryonic vertebrate limb in high-density culture undergo chondrogenic pattern formation, which results in the formation of regularly-spaced “islands” of cartilage analogous to the cartilage primordia of the developing limb skeleton. In this article we describe a discrete, agent-based stochastic model for studying the behavior of limb bud precartilage mesenchymal cells in vitro. This model, like an earlier one, employs a biologically motivated reaction-diffusion process and cell-matrix adhesion as the basis of self-organizing pattern formation, but constitutes an improvement in biological fidelity over previous descriptions in that it is multiscale (i.e., cell and molecular dynamics occur on distinct scales), and the cells are represented as spatially extended objects. The improved model reproduces a broader set of results of the micromass culture system than the previous one and discloses multiple dynamical regimes that suggest new biological experiments.

The authors acknowledge support from the National Science Foundation (IBN-0344647). We thank the reviewers for their comments and suggestions.