A Multiscale Modeling Approach for Large Deformation Behavior of Erythrocyte Membrane

本研究的目标是开发一种微观力学模型框架，将红细胞(红细胞)细胞骨架膜的大变形行为与其详细的结构和单个蛋白质的大分子行为联系起来。红细胞细胞骨架膜是一种特殊的材料体系，它将流体类脂双层与橡胶状支架蛋白网络结合在一起，形成可承受大变形的柔性膜。最近对疾病红细胞的研究表明，膜结构和单蛋白大分子行为在决定红细胞的形状和变形性从而决定其生理功能方面起着至关重要的作用。然而，以往用连续介质力学研究细胞骨架膜的形状和变形时，忽略了关于细胞骨架膜结构的详细信息。因此，不能建立结构-变形性关系。在拟议的工作中，将开发一个基于红细胞细胞骨架膜结构的细观力学建模框架。微观力学表示的体积单元将被模拟为通过连接单元(整体蛋白质)连接到两层膜(脂双层)上的橡胶膜(骨架蛋白网络)。通过模拟疾病条件下红细胞结构变化的参数研究，探讨红细胞细胞骨架膜大变形行为的结构-功能关系。这项研究将为建立基于结构的本构模型来描述红细胞的大变形行为提供新的思路，并将极大地有助于探索疾病条件下红细胞变形的分子机制。将纳米力学与生命科学的新知识相结合的方法论有望为生命的奇迹带来新的见解，并最终导致革命性的新疗法和人类健康的改善。此外，拟议的工作和拟议的教育计划将加强纳米技术和生物技术方面的高等教育，并将激励年轻科学家和工程师在这一令人兴奋的领域发展他们的职业生涯。

The goal of the proposed research is to develop a micromechanical modeling framework that links the large deformation behavior of erythrocyte (red blood cell) cytoskeleton membrane to its detailed structure and single protein macromolecule behaviors. The erythrocyte cytoskeleton membrane is an extraordinary material system that combines a fluidic lipid bilayer with a rubber-like scaffolding protein network to form a flexible membrane that can undergo large deformation. Recent studies on the diseased red blood cells indicate that the membrane structure and the single protein macromolecule behaviors play a critical role in determining the shape and deformability, and thus the physiological functions of red blood cells. However, previous studies on the shape and deformation of cytoskeletal membrane using continuum mechanics neglect the detailed information about the structure of the cytoskeleton membrane. As a consequence, the structure-deformability relationship cannot be established. In the proposed work, a micromechanical modeling framework that is based on the structure of erythrocyte cytoskeleton membrane will be developed. The micromechanically representative volume element will be modeled as a rubbery membrane (skeletal protein network) attached to two membrane layers (the lipid bilayer) via connecting elements (integral proteins). Parametric studies which simulate the structure change of red blood cell under diseased conditions will be conducted to investigate the structure-function relationship of large deformation behavior of erythrocyte cytoskeleton membrane. The proposed research will inspire new concepts for developing a structure based constitutive model to describe the large deformation behavior of red blood cells, and will greatly assist the exploration of the molecular mechanism of red blood cell deformations under diseased conditions. The methodology of combining nanomechanics with the new knowledge in life science is expected to bring in new insight into the miracle of life and eventually result in revolutionary new therapy and improvement of human health. In addition, the proposed work, together with proposed education plans, will enhance higher education in nanotechnology and biotechnology and will inspire young scientists and engineers to develop their careers in this exciting field.