Angiogenesis is fundamental biologic process involved in development, tissue repair and tumor neovascularization. Most contemporary experimental approaches have focused on molecular mechanisms with varying results. We have focused on an alternative, and likely complementary, approach is to investigate the micro-mechanical forces that are involved in triggering angiogenesis. Empirical clinical evidence suggests that externally applied micro-mechanical forces can stimulate microvessel dilatation and even microvessel replication. Our experimental evidence investigating intussusceptive (nonsprouting) angiogenesis suggests that these clinical observations reflect fundamental mechanisms of physiologic force transduction. The ultimate goal of this project is the explanation and predictive control of physiological force transduction;that is, gain insights into how physiologic force transduction triggers intussusceptive angiogenesis in a variety of areas including development, tissue regeneration and tumor regeneration. Ultimately, this insight might be applied to applications that range from the stimulation of tissue regeneration in healing wounds in the chronically ill, and to the inhibition of tumor neovascularization to treat cancer growth and metastasis.