Mechanical Aspects of Angiogenesis

SIMPLE SUMMARY: The formation of new blood vessels from already existing ones is a process of high clinical relevance, since it is of great importance for both physiological and pathological processes. In regard to tumors, the process is crucial, since it ensures the supply with nutrients and the growth of the tumor. The influence of mechanical factors on this biological process is an emerging field. Until now, the shear force of the blood flow has been considered the main mechanical parameter during angiogenesis. This review article provides an overview of further mechanical cues, with particular focus on the surrounding extracellular matrix impacting the cell behavior and, thus, regulating angiogenesis. This underlines the enormous importance of the mechanical properties of the extracellular matrix on cell biological processes and shows how changing the mechanics of the extracellular matrix could be used as a possible therapeutic approach in cancer therapy. ABSTRACT: Angiogenesis is of high clinical relevance as it plays a crucial role in physiological (e.g., tissue regeneration) and pathological processes (e.g., tumor growth). Besides chemical signals, such as VEGF, the relationship between cells and the extracellular matrix (ECM) can influence endothelial cell behavior during angiogenesis. Previously, in terms of the connection between angiogenesis and mechanical factors, researchers have focused on shear forces due to blood flow. However, it is becoming increasingly important to include the direct influence of the ECM on biological processes, such as angiogenesis. In this context, we focus on the stiffness of the surrounding ECM and the adhesion of cells to the ECM. Furthermore, we highlight the mechanical cues during the main stages of angiogenesis: cell migration, tip and stalk cells, and vessel stabilization. It becomes clear that the different stages of angiogenesis require various chemical and mechanical cues to be modulated by/modulate the stiffness of the ECM. Thus, changes of the ECM during tumor growth represent additional potential dysregulations of angiogenesis in addition to erroneous biochemical signals. This awareness could be the basis of therapeutic approaches to counteract specific processes in tumor angiogenesis.