Non-Technical Abstract This award by the Biomaterials program in the Division of Materials Research to the University of California at Santa Barbara (UCSB) is to develop a comprehensive understanding of the nature of forces between biological protein molecules derived from neurons and how these forces, in turn, are responsible for creating the variety of different architectures found in neurons. Each different structure is responsible for a well-defined cell function including molecular mechanisms that cells use to communicate. The significance of the project is that the knowledge gained from the experimental results will allow one to begin the process of clarifying the underlying molecular causes for the disruption of the cytoskeletal structures inside neurons, a condition that leads to cell degeneration. This gained knowledge will allow the larger scientific community to design strategies to prevent cell deterioration. The research activity is designed to educate and train graduate and undergraduate students, and postdoctoral researchers in modern scientific and engineering methods and for participants to acquire skills needed for careers in academe, national laboratories, and industry. Investigators of this project are involved in a broad range of UCSB Outreach Programs with community colleges, and colleges and universities outside of Santa Barbara. These include, the NSF funded Materials Research Science and Engineering Center outreach program, the Research Internship in Science and Engineering, the Future Leaders in Advanced Materials Program, the California Alliance for Minority Participation, and the Research Experience for Teachers.
The goal of the proposal is to develop a fundamental understanding of structures, interactions, and phase behavior in co-assembling mixtures of cytoskeletal proteins, with compositions of mixtures spanning the range found in distinct compartments of neurons. A set of experiments utilizing modern X-ray-Osmotic Pressure techniques are focused on clarifying the separate roles of selected cytoskeletal associated proteins in mediating interfilament forces that result in filamentous assemblies closely related to the higher-order structures found in axons and dendrites. A separate series of experiments will explore how multivalent counterions, in particular, those that are found in cellular environments, restructure the in-vitro assembled cytoskeleton. A significance of the project is that the acquired data are expected to result in fundamentally new insights relating intermolecular interactions to heterogeneously assembled structures found in different parts of neurons. Furthermore, the studies will lead to a transformative shift in understanding of biological polymer phase behavior in the presence of multivalent ions, a nascent field of high current interest in biological physics and biomaterials. The proposed biomaterials and biophysics program is multidisciplinary and educates and trains graduate and undergraduate students, and postdoctoral researchers in modern methods required to address problems at the interface between physics, chemistry, engineering and biology. The acquired skills prepare the trainees for careers in academe, national laboratories, and industry.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
