Mechanics Characterization of Cellular Force Regulation

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DESCRIPTION (provided by applicant): This is a resubmission of an application for a career development award for Dr. Guy M. Genin in collaboration with Dr. Elliot L Elson. Dr. Genin is a Mechanical Engineering professor at Washington University in St. Louis (WU) who aims to shift his career towards quantitative biology. Dr. Elson heads a vigorous research program at WU aimed at developing viable bioartificial tissues, and is supported by the NIH. The focus of the 5-year research and training program is developing expertise in applying solid mechanics concepts to study active force regulation by cells in bioartificial tissues. Initially, Dr. Genin plans an intensive program of coursework and formal didactic study, coupled with laboratory work. After two years of study, the applicant plans a sabbatical year in Dr. Elson's lab, collaborating on mechanical characterization of idealized tissue constructs. In the final two years, the applicant would continue to collaborate on studies relating macroscopic tissue behavior and microscopic cellular behavior. By the end of the research and training plan, Dr. Genin would be situated to become a leading partner in interdisciplinary studies of cell and tissue engineering at WU, and supported by the NIH. The research plan aims to quantify the relationship between cellular behavior and tissue behavior in idealized tissue constructs. This is vital for developing artificial tissues whose mechanical properties mimic those of the healthy tissues they replace, and for determining the mechanical response of cells in vivo. The primary analytical tool with which the applicant will begin these studies is an improved constitutive model for bioartificial tissues (Aim 1). The work will also require careful study of remodeled collagen (Aim 2.) The applicant will proceed to study progressively more complicated tissue constructs: first, reconstituted collagen populated with cardiac fibroblasts (Aim 3), and then a similar tissue populated with cardiac fibroblasts and cardiomyocytes (Aim 4.)