Structure-Based Mechanical Modeling of Basement Membrane

描述（由申请人提供）：基底膜是普遍存在的和必需的，作为许多重要的内皮、上皮和可兴奋组织的支架。由于它们的重要性，基底膜被非常好地研究。虽然实验研究已经产生了很多关于基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，我们提出了一种新的方法来探索基底膜结构，使用先进的计算方法，以提供一个关于基底膜结构的假设和基底膜行为的实验测量之间的桥梁。该方法将在基底膜中IV型胶原蛋白网络的一系列日益复杂的模型上实施，并将使用多尺度建模方案来基于微观结构预测宏观行为。为了与R21计划的重点，探索性使命保持一致，我们的目标是实施拟议的计划，并评估它是否是可行的研究工具。 该项目直接关系到公共卫生，因为对基底膜结构和功能的了解可以提供对器官功能和疾病治疗的了解。此外，拟议研究中确立的原则可以为医疗应用生物材料的开发提供信息。该项目直接关系到公共卫生，因为对基底膜结构和功能的了解可以提供对器官功能和疾病治疗的了解。此外，拟议研究中确立的原则可以为医疗应用生物材料的开发提供信息。

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.