Enhancing Cardiac Myosin Function with an Abiotic Energy Source

Cardiac myosin is the force generating molecular motor of heart making it a potential target to improve cardiac function in failure patients. We sought enhance and motion capacity porcine vitro by replacing ATP with azobenzene triphosphate (AzoTP), an abiotic synthetic energy source. In motility assay translocated actin filaments 50% faster using this compound compared (1.7 ± 0.09 vs. 1.2 µm ∙ s-1, p<0.05). also measured effect on myosin's force-generating mini-ensemble (∼10 heads) three-bead laser trap assay. Preliminary findings suggest that when ortho-AzoTP substrate generates more than twice as does (0.69 0.01 0.30 pN respectively). To begin delineate mechanism increased velocity we filament concentration found at half-maximal activation was dramatically reduced suggesting has affinity for (400 1223uM). The saturating may be result accelerated rate ortho-AzoDP-release from active site. Additionally, frequency binding events much greater (5 2Hz), increase due attachment filament. Thus, these demonstrate alternative can myosin. A deeper investigation mechanisms underlying enhancement reveal novel approaches pathological conditions such failure.