The proposed work attempts to describe physical laws which govern morphogenesis and wound healing, areas of direct relevance to clinical research and human health. The proposed morphomechanical law states that tissue, when subject to mechanical stress, responds according to either the hyper-restoration (HR) or the stretch activation (SA) response, and the rate of stress is the factor which determines the response regime. When stress is gradually applied to tissue, it will actively deform (grow or contract) so that the internal stress returns to the original value and then overshoots it. This is the HR response, and it can iteratively produce rich morphogenetic patterns in developing embryos. The SA response takes place in rapidly stretched or shortened tissue, which is predicted to actively contract or elongate, respectively, relative to its current stress-free state. Finally, the molecular signal for the SA response is hypothesized to be a brief intracellular calcium concentration spike triggered by rapid cell deformation. Lacking this calcium signal, the cells generate the HR response.
The specific aims of the proposed research are, 1. Determine the morphomechanical laws which govern the active response of embryonic epithelial tissue to dynamic loads. Small explants of tissue will be stretched under microactuator control to measure its response to deferent stretching rates and to obtain its morphomechanical parameters. 2. Test morphomechanical laws in tissue wounding experiments. Small circular incisions will be made in unexcised chick embryo epithelia and the rate of wound closure quantified. In addition, a finite element model of the tissue will be constructed using the hypothesized morphomechanical laws and parameters obtained from aim 1. The model will be verified by comparison with experimental results. 3. Determine biochemical-signaling pathways, which govern tissue response. Both stretching and wounding experiments will be repeated in the presence of various reagents, whose elect on the morphomechanical parameters will be used to deduce the molecular signal governing the two response regimes.
. How do tissues react when they are stretched or compressed, for instance in a growing body or in an injury? The proposed research seeks to understand how tissues grow and deform in response to mechanical forces, with the goal of better treatment of wounds and birth defects.