Eukaryotic biological motions across scales and orders of magnitude involve cytoskeleton elements. Because of their importance in cell division, motility and muscle contraction, mutations in cytoskeleton are frequently associated with human pathology e.g., cardiomyopathies, neurological syndromes and ciliopathies. Our lab is focused on understanding how cytoskeleton assemblies coordinate during physiological and their deregulation during disease conditions. In this talk I will highlight work from our lab, which utilizes the power of nanoengineering (protein and DNA engineering) and in vitro reconstitution to uncover new findings in motility systems mediated by cytoskeleton elements.