Biomolecular Materials: Structure, Phase Behavior, & Interactions

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Nontechnical: This award by the Biomaterials program in the Division of Materials Research to the University of California at Santa Barbara (UCSB) aims at discovering and understanding the structures that form inside neurons. The protein-based skeletal structures inside nerve cells are multifunctional; for example, they give mechanical stability to neurons while at the same time enabling efficient transport of molecules (e.g. neurotransmitters) from the cell body to the synapse region, which is a critical function and enables communication between neurons. The cell free studies of this project, with carefully selected neuron-derived proteins (and variations of the proteins), will lead to the identification of protein components that assemble correct or aberrant cytoskeletal structures. The studies are important since aberration in the cytoskeleton structure invariably leads to neurodegeneration. The research team members are all involved in the educational training components of the project, through Science and Engineering internship outreach programs at the UCSB. Undergraduate students from UCSB, and summer intern undergraduates from community colleges as well as national colleges and universities participate in this program. The research team's outreach activities also extend to mentoring and providing education and research experience to teachers from local high schools.Technical: This award is to develop a scientific understanding of the out-of-equilibrium phase behavior and structures in mixtures of tubulin, microtubules, and microtubule-associated-proteins derived from neurons. The functional significance of the heterogeneous dynamical microstructures observed in different neuronal compartments (i.e. axon, cell body, and dendrites) is poorly understood. Thus, the significance of the cell free studies is that they will enable scientists to develop an understanding of how different proteins derived from neurons contribute to distinct structures observed in vivo, and how these structures enable functions including mechanical stability and facilitated transport within neurons. The project will impact several nascent fields of biomaterials, including (1) intrinsically-disordered-proteins where the studies will lead to a mechanistic understanding of the role of unstructured proteins in hierarchical assembly, and (2) non-equilibrium biomaterials where the studies are expected to discover new protein structures due to the local dissipation of energy (as it happens in cells). The project offers excellent opportunities for the educational training of students (both undergraduate and graduate) in cutting-edge structural research techniques including synchrotron small-angle-x-ray-scattering and electron microscopy at US National facilities.