Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p

Climate change and coastal vulnerability assesment: scenarios for integrated assessment

Coastal vulnerability assessments still focus mainly on sea-level rise, with less attention paid to other dimensions of climate change. The influence of non-climatic environmental change or socio-economic change is even less considered, and is often completely ignored. Given that the profound coastal changes of the twentieth century are likely to continue through the twenty-first century, this is a major omission, which may overstate the importance of climate change, and may also miss significant interactions of climate change with other non-climate drivers. To better support climate and coastal management policy development, more integrated assessments of climatic change in coastal areas are required, including the significant non-climatic changes. This paper explores the development of relevant climate and non-climate drivers, with an emphasis on the non-climate drivers. While these issues are applicable within any scenario framework, our ideas are illustrated using the widely used SRES scenarios, with both impacts and adaptation being considered. Importantly, scenario development is a process, and the assumptions that are made about future conditions concerning the coast need to be explicit, transparent and open to scientific debate concerning their realism and likelihood. These issues are generic across other sectors