Control of Eukaryotic Cell Migration Through Modulation of Extracellular Chemoattractant Gradients

Cell migration is fundamental to a wide range of biological and physiological functions including: wound healing, immune defense, cancer metastasis, as well as the formation and development of biological structures such as vascular and neural networks. In these diverse processes, cell migration is influenced by a broad set of external mechanical and biochemical cues, particularly the presence of (time dependent) spatial gradients of soluble chemoattractants in the extracellular domain. Many biological models have been proposed to explain the mechanisms leading to the migratory response of cells as a function of these external cues. Based on such models, here we propose approaches to controlling the chemotactic response of eukaryotic cells by modulating their micro-environments in vitro (for example, using a microfluidic chemotaxis chamber). By explicitly modeling i) chemoattractant-receptor binding kinetics, ii) diffusion dynamics in the extracellular domain, and iii) the chemotactic response of cells, models for the migration processes arise. Based on those models, optimal control formulations are derived. We present simulation results, and suggest experimental approaches to controlling cellular motility in vitro, which can be used as a basis for cellular manipulation and control.