NER: Dynamics of Flagellar Polymorphism

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This is a Nanoscale Exploratory Research award. The general idea is to understand the mechanism by which bacterial flagella "switch" between rotating clockwise and rotating counterclockwise, with the longer-term goal of using this information to develop nanoscale switches that can be used in practical or commercial applications. Bacterial flagella are remarkable structures, nanometers in diameter, that possess mechanical and dynamical properties unlike any known material on the macroscale. Composed of eleven filaments self-assembled from the protein flagellin, they may interconvert between multiple helical morphologies of both left-and right-handedness as a consequence of monomer conformational transitions that change packing properties on the subnanometer scale. These minute molecular rearrangements have important consequences for cellular dynamics on a range of larger scales, especially so in cellular motility. During chemotaxis, the multiple rotating flagella that provide thrust to the cells bundle and unbundle as their rotary motors, embedded in the membrane, episodically change rotational direction. When bundled, the bacterium moves linearly; disintegration of the bundle upon motor reversal creates a tumbling event that randomizes the cell's orientation. These motions of "run "and "tumble "produce the random walks that underlie chemotaxis. The motor reversal also initiates a propagating chirality reversal, turning a left-handed helix that had been rotated counterclockwise into a right-handed helix rotated clockwise. These interconversions occur not only from the torques of rotary motors, but may also be triggered by fluid flow past flagella.Little is known experimentally about the nanomechanical properties of flagella and especially of dynamic polymorphism. Very recently, Dr. Goldstein and his collaborators developed the first theoretical model that explains the early, mostly qualitative, experiments on chirality transitions produced by external flows. This continuum model incorporates monomer packing multistability into a novel nonlinear extension of elasticity theory, coupled via slender-body hydrodynamics to fluid flow. In this way, it connects conformational transitions at the nanoscale to dynamics at the cellular scale, and captures many of the key features of those experiments. It also makes a number of sharp predictions regarding the initiation, frequency, and velocity of chirality transformations, to date untested. This project will use recent, important developments in fluorescent imaging methods for flagella, coupled with optical trapping methods, to conduct the first experiments on flagella under well-defined and controllable conditions of fluid stress or external forces, creating a "low Reynolds number wind tunnel" for flagellar dynamics. Concurrently, Drs. Goldstein and Kessler will extend the theoretical approach to make quantitative contact with these experiments, using the latest techniques they have developed for the study of the coupled partial differential equations that describe overdamped bending and twisting of elastic filaments. These studies will yield important information about the stress-induced conformational transitions underlying polymorphism at the nanoscale, and perhaps open the way toward the use of these molecular switches in microfluidics or MEMS applications.