Extracellular Matrix Stiffness Modulates Microvascular Morphology During Early Sprouting Angiogenesis In Vitro

Sprouting angiogenesis is associated with changes in matrix stiffness[1]. Neovessel growth and morphology are in turn affected by the changes in matrix orientation or forces acting on the matrix[2]. Matrix rigidity influences the formation of cord like structures[3, 4] and could play a role in development of tissue specific vascular morphology or inhibit cellular functions in diseases. The effect of matrix stiffness on neovessel growth from preformed vasculature has not been examined. Matrix stiffness could be increased both by an increase in matrix density[5] as well as increased crosslink formation, as in hyperglycemia[6]. It is thus essential to first identify the effect of increase in local stiffness alone, in the absence of artificially induced crosslinks, which may interfere with matrix orientation. Our aim is to characterize changes in early angiogenesis associated with ECM of different densities and relate these to changes in matrix orientation.