BECS: Pattern Formation by Vascular Stem Cells: Control of Complex Biological Systems through Bottom-up and Top-down Approaches

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

This project studies the mechanisms by which vascular-derived stem cells spontaneously organize into patterns, and then uses these mechanisms to devise some simple controls on pattern formation. Building on our previous work using Partial Differential Equation models of the developing stem cell culture system, we will develop a series of predictions addressing how altered boundary conditions change the occurrence, size, shape and other parameters of the pattern. We will extend our previous modeling efforts by incorporating cells and cell movement in the model, which had previously been purely chemical. We will also study how the mechanical and chemical properties of the substrate alter the evolving pattern, and how the features of cell proliferation and movement affect the pattern. Predictions will be tested in an experimental culture system of vascular-derived adult stem cells. The process by which cells self-organize into structured patterns ("pattern formation") is essential to many biological processes. The development of the embryo, for example, can be viewed as a sequence of these processes. It is clearly important to understand the mechanisms of these processes in order to be able to do successful ?tissue engineering?. In the past, a common approach to tissue engineering has been to decide what patterns are desired, and then to attempt to use direct external controls to produce that pattern, without an understanding of the underlying biological organizational principles. However, biological systems are characterized by their capacity for self-organization, which can defeat and frustrate direct attempts at pattern control. Here, we propose to take advantage of the self-organizational behavior of stem cells to derive engineering approaches to the inverse problem of coaxing complex biological systems into a desired form. We believe that the shape of the boundary, the elastic and chemical properties of the surface on which they are grown, and the migratory tendencies of the cells are important contributors to pattern formation. We expect that insights gained from this study will have a positive impact on attempts to achieve tissue engineering of biological complex structures.