Collaborative Research: Developing A Complete Membrane-Cytoskeleton Model for Human Erythrocyte

合作研究：开发完整的人类红细胞膜细胞骨架模型

• 批准号: 1067523
• 负责人: Sulin Zhang
• 金额: $ 20万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1067523&HistoricalAwards=false
• 关键词: Collaborative; Research; Developing; Complete; Membrane

1067523/1066469Zhang/LiDuring its 120-day life span, a human red blood cell (RBC) circulates a million times in human body and often squeezes through narrow capillaries, exhibiting an amazing ability of control over its shape and mechanical properties under external mechanical stimuli. This collaborative project aims to develop a complete human RBC model coupling the coarse-grained membrane model and cytoskeleton model and to study the molecular regulatory mechanisms in RBC deformation. The complete RBC model is molecularly based, and thus faithful to the underlying nano-scale architecture of the RBC. Upon validation against existing analytical and experimental studies, the complete RBC model will be employed to identify molecular origins of RBC deformation and disorders under combined metabolic activation and mechanical loading.The intellectual merit of this project resides in the development of the first ever computational whole-cell platform for human erythrocyte. The coarse-grained modeling will establish a direct link between nanostructural changes and observables such as fluctuation, shape, and disorders. When integrated with existing microscopic models of key components in living cells, such as actin and focal adhesion complex, the computational whole-cell platform established herein will help foster transformative progress for the analysis of RBC responses in particular and cell mechanics in general.The first-ever computational whole-cell platform built upon a detailed blueprint of all the nanostructural members of an entire RBC cell at nanometer resolution will have a revolutionary impact on computational cell biology. The computational platform facilitates identifying the molecular origins of RBC disorders, presenting another key impact of the proposed project. The educational program will enhance minority involvement and participation in science and engineering, and stimulate the interests of students in Penn State and MIT in the emerging field of multiscale modeling of cell mechanics.

1067523/1066469 Zhang/li人红细胞在其120天的寿命中，在人体内循环100万次，经常挤过狭窄的毛细血管，在外部机械刺激下显示出惊人的控制其形状和机械性能的能力。这项合作项目旨在建立一个完整的人红细胞模型，将粗粒膜模型和细胞骨架模型结合起来，研究红细胞变形的分子调控机制。完整的RBC模型是基于分子的，因此忠实于RBC的底层纳米级结构。在与现有的分析和实验研究相比较的基础上，完整的RBC模型将被用来确定在代谢激活和机械载荷联合作用下RBC变形和紊乱的分子起源。该项目的智力优势在于开发了第一个用于人类红细胞的计算全细胞平台。粗粒度建模将在纳米结构变化和诸如涨落、形状和无序等可观测性之间建立直接联系。当与现有的活细胞中关键成分的微观模型，如肌动蛋白和焦点黏附复合体相结合时，这里建立的计算全细胞平台将有助于促进对RBC反应特别是一般细胞力学的分析的变革性进展。首次建立在纳米分辨率的整个RBC细胞的所有纳米结构成员的详细蓝图上的计算全细胞平台将对计算细胞生物学产生革命性的影响。该计算平台有助于确定RBC疾病的分子起源，展示了拟议项目的另一个关键影响。该教育计划将加强少数群体对科学和工程的参与，并激发宾夕法尼亚州立大学和麻省理工学院学生对新兴的细胞力学多尺度建模领域的兴趣。