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

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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.