Chirality and Entropy in Self-Assembly of Biopolymers

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INTELLECTUAL MERIT: The proposal has four experimental aims organized around the common themes of entropy and chirality and how these affect interactions between, and self-assembly of, biopolymers. The first aim will focus on measuring the mesoscopic potential between a pair of actin filaments held together in part by entropic (depletion) forces. The goal is to determine the contribution of entropic fluctuations to the attraction between the filaments. Two alternative approaches will be used. In one, a laser tweezer is used to pull a pair of filaments apart in combination with a fluorescence microscope to image the system simultaneously. The attractive forces can be extracted directly from this experiment. An alternative approach analyzes images of isolated filaments which fold on themselves in hairpin fashion. The adhesion energy is determined by recognizing that it is balanced against the elastic energy stored in the folded filament to determine the size of the hairpin loop. The second aim is to study the self-assembly of monodisperse non-rodlike viruses into colloidal membranes, a phenomenon recently observed in the PI's laboratory. These virus particles do not exhibit the polarized head-tail amphilicity characteristic of most membrane formers, and this membrane assembly process is thus hypothesized to be driven by depletion forces. The third experiment examines the effects of chirality on the formation of colloidal membranes and twisted ribbons using both chiral and achiral filamentous viruses. This work explores the hypothesis that formation of ribbons is driven by the molecular chirality of the constituent rods. The final project examines extensions of the theories of the excluded-volume-driven transition of rodlike particles to a nematic phase at modest rod densities. Here it is planned to examine the role of chirality in the rods to explain the observed chiral nematic (cholesteric) phase often observed in these systems. In all of these studies the primary experimental tool is a multimode microscope that can acquire images in differential interference contrast and fluorescence modes. This is coupled with a laser tweezer to exert force on colloidal beads or other structures with high refractive index and determine the position of the beads with nanometer precision on a microsecond timescale.BROADER IMPACTS: The proposal is highly interdisciplinary in nature and will provide new design principles for assembling complex biomaterials. The PI is developing a new advanced laboratory course in quantitative biology instrumentation, which will focus on the design and application of modern microscopy. This course is also the centerpiece of a larger effort at Brandeis, partially supported by the Howard Hughes Medical Institute and an NSF-IGERT grant, to establish an interdisciplinary graduate program in Quantitative Biology. The project will provide a platform for training of two graduate students. Funds are also included in the award to support two undergraduate students per year on the project.