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

1067523/1066469 Zhang/Li在120天的生命周期中，人体红细胞（RBC）在人体内循环了100万次，经常在狭窄的毛细血管中挤压，在外部机械刺激下表现出惊人的控制其形状和机械性能的能力。该合作项目旨在建立一个完整的耦合粗粒膜模型和细胞骨架模型的人红细胞模型，并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进行验证后，完整的红细胞模型将用于确定红细胞变形和在代谢活化和机械负荷组合下的紊乱的分子来源。该项目的智力价值在于开发有史以来第一个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可观测量（如波动、形状和无序）之间建立直接联系。当与活细胞中关键成分的现有微观模型（如肌动蛋白和粘着斑复合物）相结合时，本文建立的计算全细胞平台将有助于促进特别是RBC反应和一般细胞力学分析的变革性进展。细胞平台建立在整个红细胞细胞的所有纳米结构成员的详细蓝图上，以纳米分辨率将对计算细胞生物学产生革命性的影响。计算平台有助于识别RBC疾病的分子起源，这是拟议项目的另一个关键影响。该教育计划将加强少数民族参与和参与科学和工程，并激发宾夕法尼亚州立大学和麻省理工学院学生对细胞力学多尺度建模这一新兴领域的兴趣。

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.