The research goal of this career-development plan is to build a theoretical framework for quantitative exploration of the effects of transmembrane protein interactions on the formation and stability of membrane structures in cell organelles. This study is primarily motivated by a number of recent experiments that show clearly that specific proteins can interact adhesively, providing a sort of "glue" that can reconfigure and stabilize the highly compact and regular structure of membranes in endoplasmic reticula, Golgi apparatus, and mitochondria. This grant will enable the development of theoretical and computational models based on continuum mechanics and the finite-element method, which will be used to address physical questions prompted by this hypothesis; namely, what structural motifs arise as energy-minimizing equilibrium structures of compact membranes decorated with adhesive proteins, and are such adhesive interactions mechanically sufficient to generate the membrane structures observed in organelles? Integrated with the proposed research plan will be a group of educational activities designed to expose graduate and undergraduate students in engineering to the highly interdisciplinary world of biophysics, and simultaneously to reach outside of engineering to students and faculty in the broader biophysics community by introducing them to the powerful mathematical and computational tools of engineering continuum mechanics.
The ultimate future impact of a more complete biophysical understanding of organelle mechanics will be the enabling of new medical techniques and treatment of diseases marked by changes in organelle structure. The immediate impacts of this plan will be (1) the training of university undergraduate and graduate students through interdisciplinary course-work, and collaborative research in mechanics and biology; (2) outreach to students from underrepresented groups through opportunities in undergraduate research; and (3) the dissemination of novel open-source software tools to other researchers in the community who seek to understand the mechanics of biomembranes.
