Molecular motors lie at the heart of biological processes ranging from DNA replication to cell migration. Engineering biomolecular motors can provide direct tests of structure-function relationships, new tools for controlling cellular processes, and customized components for harnessing molecular transport in artificial systems. Our laboratory has designed and characterized a series of modified cytoskeletal motors that reversibly change gears — speed up, slow down, or switch directions — when exposed to external signals such as metal ions or blue light. Using a modular approach, we have developed controllable motors for both actin-based and microtubule-based transport. To enable precise perturbations of mechanical functions, we have recently worked to expand the functional range of optically controlled myosins, creating next-generation designs with optimized velocities and deep modulation depths. We have also designed and tested myosin motors that incorporate rigidly attached lever arms constructed from RNA, forming hybrid assemblies in which conformational changes in protein motor domains are amplified and redirected by nucleic acid structures. Following principles established in protein engineering studies, the RNA lever arm geometry determines the speed and direction of motor transport, and can be dynamically controlled using programmed transitions in lever arm structure. Using in vitro assays of propelled actin filaments and single-molecule tracking of processive complexes, we have confirmed the operation of RNA-myosin motors designed to reverse direction under the control of strand-displacement reactions. The sequence addressability of RNA lever arm structures will allow multiplexed control of speed and direction in collections of engineered motors, enabling programming of complex transport systems. Together, an extended set of optogenetic motors and RNA-protein hybrid motors will provide a diverse toolkit for spatiotemporal control of nanoscale transport and force generation, both in living cells and in microfabricated devices that exploit the proven capabilities of biological molecular motors.

Selected publications

1. Nat Nanotechnol. 2014, 9: 693-7.
2. Nat Nanotechnol. 2014, 9: 33-8.
3. Nat Nanotechnol. 2012, 7: 252-6.

Poster
http://www.oib.orion.ac.jp/PDF/160729ProfZevBryant.pdf