Molecular-scale Breaking due to Repeated Loading in Molecular Shuttles

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The rate at which machines degrade with use has a large impact on their value. For example, modern cars last significantly longer than cars built only thirty years ago due to diligent research into failure modes and subsequent design improvements. Nanotechnology has progressed so that we can successfully build nanomachines such as 'molecular shuttles': nanoscale transport systems powered by biomolecular motors capable of delivering molecular cargo. The goal of this project is to advance our understanding of the degradation mechanisms limiting the lifetime of these molecular shuttles. The PIs research showed that 'mileage' matters - for every thousandth of an inch of distance moved, the molecular shuttle shrank a few nanometers in length. In this research project, the PIs will investigate if the course matters as well, and let the molecular shuttles travel through increasingly curvy microfabricated tracks which puts mechanical stress on their structure and should cause them to break at increasing frequencies. These experiments will improve understanding of degradation mechanisms for nanomachines in general, enable improvement of the design of our 'molecular shuttles', and may even provide insights into how biological nanomachines degrade and age. The project will integrate undergraduate researchers and high school students, and the new insights will be integrated into a new nanobiotechnology course. Outreach activities include lab activities and lectures as part of the 'Introduction to Nanotechnology' summer course for underrepresented high school students,The project is guided by two hypotheses. Firstly, it is our hypothesis that breaking events will occur stochastically at average rates determined by mechanochemical principles. Secondly, it is our hypothesis that the overall degradation of molecular shuttles in engineered environments can be understood as a combination of breaking and shortening of the microtubule component. To test these hypotheses, we will observe microtubules moved by kinesin motors (our basic 'molecular shuttle') through microfabricated guiding structures which exert a defined amount of constant and cyclic strain on the microtubule. The outcome of the project will be a potentially transformational broadening of our perspective from the physics-inspired force spectroscopy of intermolecular bonds (measuring e.g. rupture forces) to an engineering-inspired view of an accumulation of damage as result of mechanical stress in nanomachines, which may ultimately result in fracture. More immediately, the results of the project will help the community to overcome the limited lifetime roadblock in the design of nanodevices based on biomolecular motors.