2008 Eighth Annual Beckman Scholars Symposium
Thursday Poster Session - July 27, 2006

More than 12 million Americans suffer from arterial occlusive disease. In vivo and in vitro studies have identified platelet-derived growth factor (PDGF) as the major stimulus for the abnormal vascular smooth muscle cell (VSMC) migration and proliferation during the development of the disease. However, therapies simply blocking the function of PDGF have limited success in clinical trials because the pathology of the disease is complex and highly dynamic. An engineered model system that recapitulates the biomechanical properties of the vessel was used to test the hypothesis that increased vessel stiffness during the development of the disease leads to an increase in the sensitivity of VSMCs to PDGF. The polyacrylamide based model system allows the stiffness to be systematically changed from 20 kPa to 80 kPa, a range that models the in vivo stiffness of healthy and diseased vessels, respectively. To allow cell adhesion on an otherwise non-cell adhesive substrate, a constant ligand density of 5800 molecules of GRGDSP/ ?m2, a cell adhesive peptide, was maintained. With increased substrate stiffness, VSMCs have higher levels of FAK phosphorylation, increased cell-spread area, more defined stress fibers and increased rate of proliferation. VSMCs on stiffer substrate also have increased sensitivity to PDGF-BB stimulations. This increased sensitivity is not due to increased protein level of PDGF receptor, but rather increased localization of PDGFR to the lipid raft domains in the cell membrane.