Research: Tension applied to cells during their interaction with other cells or with their environment leads to their deformation and induces changes in protein synthesis and membrane properties. Filaments in the cell such as actin and microtubules mediate the action of force through their mechanical properties and their extensive communications with cellular co-factors. Fast reorganization of cytoskeletal filaments under applied forces is required during cell migration, which is important for development and tissue repair and regeneration. Moreover, muscle cells that exist primarily to generate force all use the molecular motor comprised of actin filaments and a cellular co-factor (myosin) to produce active contraction. Microtubules are responsible for the controlled directional movement of chromosomes and other organelles within the cell, which is essential for correct cell division. Understanding, at the molecular level, the complex mechanisms whereby cytoskeletal filaments mediate force transmission and the contribution of each type of filament to the structural stability of the cell is still a challenge for modern biology. The goal of this research is to elucidate the effect of forces on the internal organization of the filaments and its connection with the large-scale mechanical behavior of filaments. Computational studies of three types will be employed (1) determination of force regimes and the resulting conformational changes that characterize the response of cytoskeletal protofilaments to force; (2) elucidation of the force-structure relationships involved in the severing of filaments by cellular factors;(3) characterization of the contributions of the topology and the chemistry of inter-chain bonds to the kinetics of polymerization and depolymerization of filaments in the presence of tension. The results of these investigations will be compared and contrasted to a wealth of experimental data on protofilaments. The new knowledge gained in this project will help provide conceptual guidance for future investigations into the identity and mechanisms of action of co-factors with crucial roles in establishing the connection between the mechanics and the chemistry of the cell.
Broader impacts: Prof. Dima's long-term career goal is to create a synergy between mentoring, teaching, and research leading to the training of the future scientific workforce. The integration of research and education will be accomplished in this project through the teaching and mentoring of undergraduate and graduate students in multiscale computational approaches to investigate large cellular systems. These activities, coupled with outreach initiatives aimed at the early introduction of scientific inquiry to middle school girls from underrepresented minorities, will prepare the next generation of diverse and broadly trained workforce. Prof. Dima's work in this project will enhance the educational infrastructure at the University of Cincinnati by improving undergraduate students' understanding of Physical Chemistry through implementing cooperative learning and incorporating research topics into lectures.
