Mechanical and structural tricks worth mimicking in extracellular matrix proteins

活细胞通过物理和化学信号感知并响应其微环境。机械相互作用被认为控制许多细胞功能，例如分裂、迁移和分化。在体内，这些相互作用是由相邻的细胞和周围的细胞外基质（ECM）纤维状网络。形成这种超分子ECM结构的单个蛋白质的行为已经被广泛研究，但令人惊讶的是，在ECM中存在的不同蛋白质所发挥的可能的协同作用下，在细胞聚集的长度尺度上单个纤维的结构和机械性质仍然难以捉摸。阐明控制ECM蛋白功能及其与活细胞相互作用的物理过程（称为机械生物学）是一个肥沃的研究领域，因为它代表了一种控制活细胞功能的新策略，可以找到许多技术应用。拟议的研究计划结合了生物物理学两个密切相关（尽管独立）领域的基础研究：（i）跨多个长度尺度的蛋白质机械生物学;（ii）制造用于长期细胞培养研究的生物学启发的3D模型系统。更具体地说，第一个领域的重点将是从分子/纤维尺度（主题1）到基质/细胞尺度（主题2）关联单个ECM蛋白和蛋白组装体的结构和机械性质。第二个领域将涉及可调3D细胞培养平台的制造，该平台模拟研究和控制细胞功能所必需的ECM构象和机械特性（主题3）。这一提议具有广泛的影响，因为3D（导电和非导电）可调ECM模拟平台代表了生物物理和生物医学研究的一种新颖而通用的工具，在生物电子学，组织工程和再生医学中具有许多潜在的技术应用。该计划也将在其能力，以促进机械生物学研究的新方法，以及提供宝贵的多学科培训，以高素质的人员（HQP）在一系列尖端技术遍布生物物理学，生物材料科学和生物工程领域。这些技能将使HQP能够满足我们不断增长的高科技产业的需求，从而加强加拿大的知识经济，并确保其研究投资的最大回报。

Living cells sense and respond to their microenvironment through physical and chemical signals. Mechanical interactions are believed to control a number of cell functions such as division, migration and differentiation. In vivo, these interactions are determined both by the adjacent cells and by the surrounding extracellular matrix (ECM) fibrillar network. The behavior of the single proteins forming such supermolecular ECM structures has been studied extensively, but surprisingly the structural and mechanical properties of individual fiberson the length scale of cellstogether with the likely synergetic roles played by the different proteins present in the ECM have remained elusive. Elucidating the physical processes that govern the function of ECM proteins and their interactions with living cells (called mechanobiology) is a fertile field of research, as it represents a novel strategy for controlling living cell functions that can find numerous technological applications.***The proposed research program combines fundamental studies in two closely interconnected (though independent) areas of biophysics: (i) mechanobiology of proteins across multiple length scales and (ii) fabrication of biologically-inspired 3D model systems for long-term cell culture studies. More specifically, the focus of the first area will be to correlate structural and mechanical properties of single ECM proteins and proteins assemblies from the molecular/fiber scale (Theme 1) to the matrix/cellular scale (Theme 2). The second area will concern the fabrication of tunable 3D cell culture platforms that mimic the ECM conformational and mechanical properties essential to investigate and control cell functions (Theme 3).***This proposal has broad ranging implications as 3D (conductive and non conductive) tunable ECM-mimicking platforms represent a novel and versatile tool for biophysical and biomedical research with many potential technological applications in bioelectronics, tissue engineering, and regenerative medicine. This program will also be transformative in its capacity to promote new approaches in mechanobiology research, as well as to offer valuable multidisciplinary training to highly qualified personnel (HQP) in a range of cutting-edge techniques spread over the fields of biophysics, biomaterials science, and bioengineering. These skills would position HQP to meet the demands of our growing high-tech industry, thereby strengthening Canada's knowledge-based economy and ensuring maximum return from its research investments.