Biomolecular Materials: Structure, Phase Behavior, & Interactions

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 0803103 PI: Safinya, Cyrus ORG: California-Santa Barbara Title: Biomolecular Materials: Structure, Phase Behavior, and Interactions INTELLECTUAL MERIT: The project aims to elucidate the nature of structures and interactions in self-assemblies of filamentous neurofilaments derived from the axonal cytoskeleton and structures of curvature stabilizing lipids. The proposal combines synchrotron small angle- x-ray-scattering (SAXS), optical and cryo-electron electron microscopy experiments with statistical mechanical theoretical investigations. One series of proposed experiments focuses on understanding the nature of interfilament interactions in neurofilament networks reconstituted from purified proteins. Neurofilaments (NFs) consist of three homopolymers NF-L, NF-M, and NF-H. Recent preliminary data from the PI?s laboratory suggest qualitatively different behavior for interfilament interactions with sidearms consisting of either NF-M or NF-H. Using the synchrotron SAXS-osmotic pressure technique, a series of direct force measurements are proposed, which when combined with complementary phase behavior studies, should result in a comprehensive understanding of the nature of the interactions between neurofilaments. The studies will be conducted in NF gel phases as a function of sidearm grafting densities in binary (NF-LH, NF-LM), and ternary (NF-LMH) mixtures. The co-PI?s group will carry out statistical mechanical studies of interactions between polyampholyte brushes mimicking the NF sidearm structure of NF-L, NF-M, and NF-H. Another set of proposed experiments is based on the PI's recent discovery of block liposomes resulting from membrane curvature stabilizing multivalent lipids. Cryogenic-TEM revealed the blocks to consist of distinctly shaped nanoscale spheres, pears, tubes, or rods. Indeed, similar membrane shape changes, occurring in vivo for the purpose of specific cellular functions, are often induced by interactions between membranes and curvature stabilizing proteins. By employing a series of lipids custom synthesized in the PI?s group, which allow for systematic variations in the shape, size and charge of the curvature stabilizing lipids (mimicking properties of more complex curvature stabilizing proteins), the proposed experiments will permit the PI to distinguish between the separate contributions of charge and lipid shape responsible for the formation of block liposomes. BROADER IMPACTS: From a broader perspective, aside from further enhancing our understanding of polyelectrolyte brushes (which remains poorly understood, both in experiment and theory), the research should enhance the understanding of structures and interactions of the axonal cytoskeleton. The nanorods and nanotubes observed in the studies of block liposomes have potential applications in the area of templating (e.g. to produce nanowires) or chemical delivery. The proposed biomolecular materials program is multidisciplinary and obligates the PIs to educate and train undergraduate and graduate students, and postdoctoral researchers in modern methodologies required to address important problems at the interface between physics, chemistry, engineering, and biology. The state-of-the-art characterization capabilities developed in the PI?s group are integrated within the UCSB Materials Research Science and Engineering Center (MRSEC) x-ray facility and open to a very wide user base comprised of over 30 groups from across campus. Students also gain familiarity with existing national research facilities. The PI and co-PI actively participate in UCSB Outreach Programs with the community colleges and colleges and universities outside of Santa Barbara, which encourage participation by under-represented groups. These programs include, the MRSEC outreach program, the Internships in Nanosystems Science and Engineering Technology (INSET) outreach program, and the Research Experience for Teachers (RET) outreach program. These programs allow the PIs to train and educate undergraduate students and high school teachers in multidisciplinary methods of science and engineering.