Engineering Approaches to Biomolecular Motors

Engineering Approaches to Biomolecular Motors: From in vitro to in vivo Wednesday Speaker Abstracts

Molecular Machinery from DNA Andrew J. Turberfield . University of Oxford, Oxford, United Kingdom.

By exploiting programmable, sequence-dependent base-pairing interactions it is possible to design and build three-dimensional DNA scaffolds, to attach molecular components to them with sub-nanometre precision – and then to make them move. I shall describe our work on autonomous, biomimetic molecular motors powered by chemical fuels, hybrid DNA-kinesin devices, motors that compute, and the use of synthetic molecular machinery to control covalent chemical synthesis.

A Synthetic DNA Motor that Transports Nanoparticles along Carbon Nanotubes Jing Pan, Jong Hyun Choi . Purdue University, West Lafayette, IN, USA. Intracellular protein motors have evolved to perform specific tasks critical to the function of cells such as intracellular trafficking and cell division. Inspired by such biological machines, we demonstrate that motors based on RNA-cleaving DNAzymes can transport nanoparticle cargoes (CdS nanocrystals in this case) along single-walled carbon nanotubes. Our synthetic motors extract chemical energy from interactions with RNA molecules decorated on the nanotubes and use that energy to fuel autonomous, processive walking through a series of conformational changes along the one-dimensional track. However, their translocation kinetics is not well understood. In this work, the translocation kinetics of individual DNAzyme motors are probed in real-time using the visible fluorescence of the cargo nanoparticle and the near-IR emission of the carbon nanotube track. This visible/near-IR single-particle/single-tube spectroscopy allows us to examine the critical parameters in the motor design that govern the translocation kinetics, including DNA enzyme catalytic core type, upper and lower recognition arm lengths, and various divalent metal cations. Combined with spectroscopic single-motor measurements, a simple theoretical model, developed within the framework of stochastic single-molecule kinetics, describes the rates of individual intermediate reactions as well as the overall single turnover reaction. Our study provides general design guidelines to construct highly processive, autonomous DNA walker systems and to regulate their translocation kinetics, which would facilitate the development of functional DNA walkers.

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