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

细胞力动力学和细胞外基质力学特性在驱动血管生成中的综合作用

• 批准号: RGPIN-2018-06214
• 负责人: Bordeleau, François
• 金额: $ 2.33万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684451
• 关键词: combined; role; cellular; force; dynamics

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.

血管生成是一个复杂的过程，其中生化和机械信号调节内皮细胞增殖和迁移。近年来，我们对内皮细胞（EC）中力的作用的理解取得了一些进展。细胞收缩性是一种重要的细胞特性，它影响细胞的正常和病理过程，包括细胞粘附和迁移。已知细胞收缩性进而受到细胞外基质（ECM）的机械性质的影响。尽管密集的努力来表征生物系统中产生的力，力和动态力学性能之间的调节关系仍然几乎是未知的。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可植入支架的新血管形成过程的能力。** 目标：该研究计划将利用我们在机械生物学和生物光子学方面的背景，研究血管生成过程中3D微环境的物理特性与细胞力生成之间的动态相互作用。该计划将解决以下主要目标：（1）研究EC力产生和相关分子控制的时间动力学，以及（2）探测工程胶原支架内的离散应变传播及其对EC行为的影响。 * 影响：我们的工作将提供新的数据的功能链接和分子控制，细胞力，ECM的机械性能之间的关系，在血管生成，可用于设计更好的组织工程支架。此外，考虑到细胞力和ECM力学之间的关系并不是EC所独有的，该项目将在机械生物学领域产生深远的影响，并为我们理解力在生理过程中的作用提供重要的见解。此外，这项工作利用了一种新的工具，这将是独一无二的在加拿大，与唯一的其他类似的系统是在范德比尔特大学。通过提高我们在使用QPOL显微镜来回答生物学问题方面的专业知识，我们的目标是实现对组织工程师以及癌症和心血管研究人员的技术转移。总的来说，该研究计划将通过提供高度跨学科的环境，帮助培养高素质的人才，他们将学习生物工程，物理学和细胞生物学方面的尖端技术，这些技术在生物技术领域备受追捧。