Design, fabrication, and operation of hybrid bionanodevices for biomedical applications

Cells are the fundamental building blocks of life. Despite their simplicity, cells are extremely versatile, performing a variety of functions including detection, signaling, and repair. While current biomedical devices operate at the organ level, the next generation will operate at the cellular level, combining the nanoscale machinery of cells with the mechanical robustness of synthetic materials in the form of new hybrid devices.;This thesis presents advances in four topics concerning the development of nanomedical devices: fabrication, stabilization, control, and operation. First, as feature sizes decrease from the milli- and microscale towards the nanoscale, new fabrication methods must be developed. A new rapid prototyping technique using confocal microscopy was used to produce freely-programmable high-resolution protein patterns of functional motor proteins on thermo-responsive polymer surfaces. Second, hybrid device operation should be temperature-independent, but most biological components have strong responses to temperature fluctuations. To counter operational fluctuations, the temperature-dependent enzymatic activity was characterized for two types of molecular motors with the goal of developing a bionanosystem which is stabilized against temperature fluctuations. Third, replacing electromechanical systems consisting of pumps and batteries with proteins that directly convert chemical potential into mechanical energy increases the efficiency and decreases the size of the bionanodevice, but requires new control methods. An enzymatic network was developed in which fuel was photolytically released to activate molecular shuttles, excess fuel was sequestered using an enzyme, and spatial and temporal control of the system was achieved. Finally, chemically powered bionanodevices will require high-precision nano- and microscale actuators. A two-part hybrid actuator was designed, which consists of a molecular motor-coated synthetic macroscale forcer and a microtubule-based stator. Methods to create and characterize the stator were developed, which can be used to optimize the force generation of the device.