Chemotaxis and Chemokinesis in 3D Macromolecular Matrices: Relevance to Angiogenesis

Angiogenesis is a complex morphogenetic process involving the coordinate migration of several cell types, including endothelial cells (EC), pericytes, and stromal fibroblasts (1-4). Angiogenesis is regulated by interactions between cells, soluble factors, and extracellular matrix components. The extracellular matrix (EM) in contact with vascular cells changes during angiogenesis in terms of its composition and structural organization. For example, ECs lining the lumen in a "resting" vessel are attached to a 2D substratum of specialized structure and composition (i.e., the basement membrane). Following exposure to angiogenic factors, endothelial cells migrate from their 2D environment into the surrounding 3D tissue stroma. Within this 3D macromolecular environment, the endothelial cells adopt an elongated "sprouting"rdo; phenotype and synthesise new EM components. Pericytes and fibroblasts are normally resident within a 3D macromolecular matrix, as provided by the vessel basement membrane and tissue stroma, respectively. Nevertheless, pericytes also form part of the newly formed vascular sprouts and fibroblasts surround and accompany these. In addition, vascular sprouts are commonly accompanied by inflammatory cells that produce proteases and cytokines, thereby contributing to further alterations in the composition of the microenvironment. The migration of ECs, pericytes, and adjacent fibroblasts during angiogenesis is directional. As new vessels move towards the source of angiogenic stimulus, they migrate into matrices of different and variable composition (e.g., during wound healing new vessels and fibroblasts invade a fibrin clot) (1-7).