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.