We propose to prepare trainees for research careers with significant impact in the field of mechanobiology by providing rigorous and coherent training that crosses disciplines and length scales. The importance of mechanical force in biology at many length scales has become increasingly clear in recent years. Cells sense and respond to the mechanical properties of their microenvironment. These mechanical properties guide cell motility, determine cytoskeletal structure, and control differentiation and gene expression. At the nanometer scale, force affects molecular configuration, and vice versa;motor proteins interact with cytoskeletal components to produce contraction or to transport cargo. Forces generated by actin polymerization drive cell migration and protrusion. In each of these examples, a biochemical process produces force, but force may also affect the underlying biochemistry. These complex, coupled interactions are important in clinical and translational science, as subcellular and cellular phenomena determine the macroscopic behavior of tissues and organs, anatomy and morphology. Conversely, as an animal or plant interacts with its macroscopic environment, its structure and mechanical properties at longer length scales affect how forces are transmitted to cells and their components. The MBnc training program will exploit Washington University's strong base of faculty and resources in these areas. It will provide pre-doctoral trainees with fundamental coursework in both biology and mechanics, and research training at the intersection of these disciplines. Support for six trainees per year is requested. Each trainee will be supported for two years, typically the third and fourth year of graduate study. Trainees who participate in this program will be prepared to perform advanced interdisciplinary research on the role of mechanics in biology across length scales, and will thus fill an important and growing need in the scientific community.
Mechanical forces play a key role in human development, disease, injury and healing. The diverse effects of mechanical factors on human health are exemplified by the enhancement of bone growth by loading, and the effects of matrix stiffness on tumor cell migration. The proposed training program will provide a comprehensive program of coursework and research experiences to prepare trainees for productive research careers focusing on the effects of physical force on biological molecules, cells, and tissues.