Smooth muscle contraction is essential to the normal function of many organ systems within the body. Therefore an understanding of its normal contractile process is required before studying disease states such as hypertension in which smooth muscle function may be abnormal. An intriguing mechanical property of smooth muscle is its ability to produce as much force per cross-sectional area of muscle as skeletal muscle with far less myosin (i.e. fewer cross-bridges). These data suggest that smooth muscle cross-bridges may generate more average force than skeletal muscle cross-bridges. Since force generation in these two muscle types is believed to result from the cyclic interaction of myosin cross-bridges with actin, smooth muscle cross-bridges may achieve a higher average force by spending a larger fraction of each cross-bridge cycle attached to actin in a high force producing state (i.e. higher duty cycle). To address this question, an in vitro motility assay will be used to directly measure both the velocity and force of a single fluorescently labeled actin filament as it slides over a myosin coated glass coverslip. This proposal begins to characterize smooth muscle force generation at the molecular level.
