Multi-scale modeling of cellular mechanics

Scientists have made great strides in understanding organism function at the cellular and molecular level.  Despite all of the disciplinary and cross-disciplinary work, there remains a relatively limited understanding of the physical and biomechanical aspects of cell function.  Yes, we know about the physical chemistry of various biomolecules.  Protein structure and the functions of isolated proteins or protein complexes have also been the subjects of much study.  However, we still know very little about how physical and/or biomechanical forces alter cell function and even less about the physical/biomechanical properties of the cell interior, let alone how changes in the physical structure are controlled and what they mean for the function of tissues and organisms. 

 

The overarching aim of our proposed study is to determine how physical and biomechanical forces alter the stresses experienced by the cell.  Specifically, we hypothesize that physical forces may alter the cytoskeletal structure of a cell and in turn the shape and elasticity of the cells.  We further hypothesize that correlating experimental measurements with mathematical or computer simulations of cell dynamics will help us to better understand how cells alter their properties in order to minimize damaging physical stresses.  We will initially focus on endothelial cells lining blood vessels which have been documented to experience a variety of physical forces.  In addition, we will also use recent experiments obtained from lung epithelial cells to expand the range of data we incorporate into the computational models of cell dynamics. Features to be included are nuclear staining/morphology, fluorescently tagged proteins that can provide information about the specific attachment sites for the cells and changes in cytoskeletal structure.   Samir Ghadiali provides the expertise in biomechanics, production of specific physical forces on cells, and experience in the computational analysis of physical stress on cells while Linda Lowe-Krentz brings endothelial cell expertise along with experience in studying endothelial cell signaling responses to chemical stress.  Ultimately, the modeling studies will make it possible to predict protective changes and understand how those cell structural changes are normally controlled.