The combined role of cellular force dynamics and extracellular matrix mechanical properties in driving angiogenesis

血管生成是一个复杂的过程，由生物化学和机械信号调节内皮细胞的增殖和迁移。近年来，我们对内皮细胞（EC）中作用力作用的理解取得了一些进展。细胞收缩性是影响细胞正常和病理过程（包括细胞粘附和迁移）的关键细胞特性。细胞的收缩性反过来又受到细胞外基质（ECM）的机械特性的影响。尽管对生物系统中产生的力进行了大量的研究，但力与动态力学特性之间的调节关系仍然是未知的。这是组织工程中一个持续存在的问题，因为它影响了我们准确重建工程疾病模型或控制植入式支架新生血管过程的能力。

Angiogenesis is a complex process where biochemical and mechanical signals regulate endothelial cell proliferation and migration. Recent years have seen several advances in our understanding of the role of forces in endothelial cells (EC). Cellular contractility is now fully appreciated as a crucial cell property that influences cell behaviors involved in both normal and pathological processes, including cell adhesion and migration. Cell contractility is known to be in turn influenced by the mechanical properties of the extracellular matrix (ECM). Despite intensive efforts to characterize the forces generated in biological systems, the regulatory relationships between forces and dynamic mechanical properties remain virtually unknown. This is an ongoing problematic in tissue engineering since it affects our ability to accurately recreate engineered disease models or control the neovascularization process of implantable scaffolds. Objectives: This research program will use our background in mechanobiology and biophotonics to investigate the dynamic interplay between the physical properties of the 3D microenvironment and cell force generation during angiogenesis. The program will address the following main goals: (1) investigate the temporal dynamics of EC force generation and associated molecular controls, and (2) probe discrete strain propagation within engineered collagen scaffolds and its influence on EC behavior. Impact: Our work will provide new data on the functional link and relationship between molecular controls, cell forces, and ECM mechanical properties during angiogenesis that can be used to design better tissue engineered scaffolds. Furthermore, considering that the relationship between cell forces and ECM mechanics is not unique to ECs, this project will have far reaching impacts in the field of mechanobiology and provide critical insights in our understanding of the role of forces in physiological processes. In addition, this work leverages a novel tool that would be unique in Canada, with the only other similar system being at Vanderbilt University. By increasing our expertise in the use of QPOL microscopy to answer biological questions, we aim to enable technological transfer toward tissue engineers as well as cancer and cardiovascular researchers. Overall, this research program will contribute to the training of highly qualified personnel by providing a highly interdisciplinary environment where they will learn cutting edge techniques in bioengineering, physics, and cellular biology that are highly sought after in the field of biotechnology.