Structure-Based Mechanical Modeling of Basement Membrane

描述（由申请人提供）：基底膜无处不在，是必不可少的，是许多重要的内皮、上皮和可兴奋组织的支架。由于它们的重要性，基底膜得到了非常充分的研究。虽然实验研究已经获得了许多关于基底膜的组成和生物学的信息，但它们的组装和结构的细节仍然难以捉摸。在这项工作中，我们提出了一种探索基底膜结构的新方法，使用先进的计算方法在基底膜结构的假设和基底膜行为的实验测量之间提供了一座桥梁。该方法将在一系列日益复杂的基底膜IV型胶原网络模型上实施，并采用多尺度建模方案，基于微观结构预测宏观行为。为了与R21计划的重点探索任务保持一致，我们的目标是实施拟议的方案并评估其作为研究工具是否可行。

DESCRIPTION (provided by applicant): Basement membranes are ubiquitous and essential, serving as the scaffold for numerous and important endothelial, epithelial and excitable tissues. Because of their importance, basement membranes are extremely well studied. Although experimental studies have yielded much information about the composition and biology of basement membranes, the details of their assembly and structure remain elusive. In this work, we propose a novel approach to explore basement membrane structure, using advanced computational methods to provide a bridge between hypotheses about basement membrane architecture and experimental measurements of basement membrane behavior. The method will be implemented on a series of increasingly-complex models of the type IV collagen network in the basement membrane, and a multi-scale modeling scheme will be used to predict macroscopic behavior based on the microscopic structure. In keeping with the focused, exploratory mission of the R21 program, our goal is to implement the proposed scheme and assess whether it is feasible as a research tool. This project relates directly to public health because insight into structure and function of basement membranes can provide insight into organ function and disease treatment. Furthermore, principles established in the proposed studies can inform the development of biomaterials for medical applications. This project relates directly to public health because insight into structure and function of basement membranes can provide insight into organ function and disease treatment. Furthermore, principles established in the proposed studies can inform the development of biomaterials for medical applications.