Protein-to-Tissue Model of Glomerular Mechanobiology

肾小球力学生物学的蛋白质到组织模型

• 批准号: 1300649
• 负责人: Victor Barocas
• 金额: $ 40万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1300649&HistoricalAwards=false
• 关键词: Protein; Tissue; Model; Glomerular; Mechanobiology

The research objective of this award is to use computational models at different length scales to develop an understanding of how changes to the proteins that form the glomerular basement membrane (GBM) of the kidney alter the mechanical properties of the basement membrane as a whole. The GBM is the major structural layer of the filtration apparatus of the kidney, so its ability to withstand high pressures and allow blood plasma to pass through it is necessary for proper kidney function. A series of models from the molecular to the tissue scale will be constructed and linked together. The stiffness and strength of the tissue will be estimated based on the protein properties, as will the permeability of the tissue (i.e., its tendency to permit filtration flow through it). Finally, changes in the properties of the tissue, coupled with the known demand for filtration, will be used to model dynamic changes in the GBM in response to changes in load or protein properties.If successful, these studies will help explain how the kidney, which filters 40-50 gallons of blood every day, performs in healthy conditions and suffers decreased performance in disease. The new understanding may help drive treatments for patients with genetic diseases that affect the kidney (e.g., Alport syndrome) and also for patients with kidney disease arising from other sources, such as diabetes. The project also involves training of a Ph.D. student in biomedical engineering and an outreach program for students interested in STEM at the College of the Menominee Nation, which will contribute to the strength and diversity of our high-tech workforce.

该奖项的研究目标是使用不同长度尺度的计算模型来了解形成肾脏肾小球基底膜（GBM）的蛋白质的变化如何改变整个基底膜的力学特性。GBM是肾脏过滤装置的主要结构层，因此它承受高压和允许血浆通过的能力对正常的肾脏功能是必要的。从分子到组织尺度的一系列模型将被构建并连接在一起。组织的刚度和强度将根据蛋白质的性质来估计，组织的渗透性也是如此（即，它允许过滤流过它的倾向）。最后，组织性质的变化，加上已知的过滤需求，将用于模拟GBM的动态变化，以响应负载或蛋白质性质的变化。如果成功的话，这些研究将有助于解释每天过滤40-50加仑血液的肾脏是如何在健康状态下工作，而在疾病状态下工作能力下降的。这一新的认识可能有助于推动对患有影响肾脏的遗传性疾病（如阿尔波特综合征）的患者的治疗，也有助于对其他原因引起的肾脏疾病（如糖尿病）患者的治疗。该项目还包括培训一名生物医学工程博士生，并为梅诺米尼民族学院对STEM感兴趣的学生提供外展计划，这将有助于我们高科技劳动力的实力和多样性。