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Modelling and engineering artificial burnt-bridge ratchet molecular motors

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Thesis type
(Thesis) Ph.D.
Date created
Nature has evolved many mechanisms for achieving directed motion on the subcellular level. The burnt-bridge ratchet (BBR) is one mechanism used to accomplish superdiffusive motion over long distances via the successive cleavage of surface-bound energy-rich substrate sites. The BBR mechanism is utilized throughout Nature: it can be found in bacteria, plants, mammals, arthropods (for example Crustaceans and Cheliceratans), as well as non-life forms such as influenza. Motivated to understand how fundamental engineering principles alter BBR kinetics, we have built both computer models and synthetic experimental systems to understand BBR kinetics. By exploring the dynamics of BBRs through simulation we find that their motor-like properties are highly dependent on the number of catalytic legs, the distance that the legs can reach from the central hub, and the hub topology. We further explore how design features in the underlying landscape affect BBR dynamics. We find that reducing the landscape from two- to one-dimensional increases superdiffusivity but leads to a loss in processivity. We also find that landscape elasticity affects all motor-like dynamical properties of BBRs: there are different optimal stiffnesses for distinct dynamical characteristics. For a spherical-hub BBR, speed, processivity, and persistence length are optimized at high, intermediate and soft stiffnesses, respectively, while rolling is also optimized at a high surface stiffness. Towards our development of a novel micron-sized protein-based BBR in the lab, we develop a new surface chemistry passivation technique and apply it to the surface of nanowires, turning an array of waveguiding nanowires into a high-throughput biosensing assay. In a separate assay, our protein-based BBR, which we call the lawnmower, is implemented in two dimensions on glass cover slips prepared with our surface chemistry (which serves as the lawn). We find the lawnmower dynamics reproduce key observations found in other similar systems, such as saltatory motion and broadly varying anomalously diffusive behaviour. The successful implementation of the lawnmower marks the first demonstration of an artificial protein-based molecular motor.
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Supervisor or Senior Supervisor
Thesis advisor: Forde, Nancy
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