Abstract: The emergence of nanotechnology as a feasible avenue for real engineering solutions has brought about innovative breakthroughs but also tremendous challenges. Recently, it has been observed that nature has developed complex systems on the nanoscale that can teach us much about device design. Most notably, the use of functionalized molecules for both actuation and fabrication has lent credence to biomimetic proof of concept studies. Synthetic molecules that can be designed and manufactured specifically for an engineered purpose, such as rotaxane, have been shown to serve as powerful actuators when working together within engineering systems. However, only after thorough single molecule characterization studies can their performance be best understood and therefore, exploited efficiently. Such a study using atomic force microscope dynamic force spectroscopy experiments agreed well with theoretical results and concluded that each molecule produces 65 kcal/mol of energy. This result is vastly superior to the performance of natural motor molecules and current engineering materials. However, it also highlights the need for support systems and architectures that integrate them into conventional systems with molecular level accuracy. As such, protocols were developed to take advantage of the highly parallel and exacting fabrication seen in the self-assembly of muscle proteins. MEMS patterned functionalized surfaces were combined with mammalian muscle proteins including actin, gelsolin and α-actinin to form a hybrid top-down/bottom-up manufacturing paradigm. Arbitrary geometries were demonstrated, producing self-assembled growth in three-dimensions. These architectures feature the control of traditional patterning techniques but the addition of natural molecules adds precision and functionality that makes for a versatile foundation on which further growth can be initiated. Consequently, the benefits of integrating functional molecules into engineering designs have been demonstrated as well as a self-assembling fabrication paradigm by which to do so.