Integration of experimental and computational approaches to sprouting angiogenesis.

PURPOSE OF REVIEW We summarize recent experimental and computational studies that investigate molecular and cellular mechanisms of sprouting angiogenesis. We discuss how experimental tools have unveiled new opportunities for computational modeling by providing detailed phenomenological descriptions and conceptual models of cell-level behaviors underpinned by high-quality molecular data. Using recent examples, we show how new understanding results from bridging computational and experimental approaches. RECENT FINDINGS Experimental data extends beyond the tip cell vs. stalk cell paradigm, and involves numerous molecular inputs such as vascular endothelial growth factor and Notch. This data is being used to generate and validate computational models, which can then be used to predict the results of hypothetical experiments that are difficult to perform in the laboratory, and to generate new hypotheses that account for system-wide interactions. As a result of this integration, descriptions of critical gradients of growth factor-receptor complexes have been generated, and new modulators of cell behavior have been described. SUMMARY We suggest that the recent emphasis on the different stages of sprouting angiogenesis, and integration of experimental and computational approaches, should provide a way to manage the complexity of this process and help identify new regulatory paradigms and therapeutic targets.