DESCRIPTION (provided by applicant): Our goal is to determine the molecular mechanisms of the myosin-I family of molecular motors. Myosin-Is comprise the largest unconventional myosin family found in humans (eight genes), and its large size and expression profile distinguish it as one of the most diverse. Myosin-Is physically link cell membranes to the underlying actin cytoskeleton where they play essential roles in powering membrane dynamics, membrane trafficking, and mechanical signal- transduction. Myosin-I's show remarkable diversity in their cellular function, which is mediated by their diverse biophysical properties, which includes dynamic tension sensing, membrane- attachment, and unique regulatory modes. Our goal is to provide the biochemical and biophysical foundation for understanding the molecular physiology of this important class of motors. We will use a combination of innovative biophysical techniques to define (1) the structural origin of myosin-I force sensing, (2) the role f myosin-I adaptor proteins in controlling myosin-I activity, and (3) control of myosin-I function by actin regulatory proteins.