A Multiscale Modeling Approach for Large Deformation Behavior of Erythrocyte Membrane

红细胞膜大变形行为的多尺度建模方法

• 批准号: 0528548
• 负责人: Hang Qi
• 金额: --
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2008-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0528548&HistoricalAwards=false
• 关键词: Multiscale; Modeling; Approach; Large; Deformation

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.

拟议的研究的目的是开发一个微机械建模框架，该框架将红细胞（红细胞）细胞骨架膜的较大变形行为与其详细结构和单蛋白大分子行为联系起来。红细胞细胞骨架膜是一种非凡的材料系统，将液体脂质双层与橡胶状的脚手架蛋白网络结合在一起，形成一种柔性膜，可以经历大变形。关于患病的红细胞的最新研究表明，膜结构和单蛋白大分子行为在确定形状和变形性方面起着至关重要的作用，因此是红细胞的生理功能。但是，先前使用连续力学的细胞骨架膜形状和变形的研究忽略了有关细胞骨架膜结构的详细信息。结果，无法建立结构可构性关系。在拟议的工作中，将开发基于红细胞细胞骨架膜结构的微机械建模框架。微机械代表性的体积元件将通过连接元件（积分蛋白）连接到两个膜层（脂质双层）上的橡胶膜（骨骼蛋白网络）。将进行模拟红细胞在患病条件下的结构变化的参数研究，以研究红细胞细胞骨架膜的大变形行为的结构 - 功能关系。拟议的研究将激发新的概念，以开发基于结构的本构模型来描述红细胞的大变形行为，并将大大帮助探索患病病情下红细胞变形的分子机制。预计将纳米力学与生命科学新知识相结合的方法将带来对生活奇迹的新见解，并最终导致革命性的新疗法和改善人类健康。此外，拟议的工作以及拟议的教育计划将增强纳米技术和生物技术的高等教育，并将激发年轻的科学家和工程师在这个令人兴奋的领域发展其职业。