Single molecule optical trap studies on actomyosin elucidate cardiovascular disease mechanisms

Heart failure due to aging, anoxic episodes and cardiomyopathies is a major health-care problem. We studied possible therapeutic interventions and several point mutations in the beta-cardiac myosin motor amino acid sequence using single molecule optical trapping technology to understand their puzzling mechanisms. Omecamtiv mecarbil (OM) ameliorates heart failure, even though it suppresses myosins mechanical working stroke by a cooperative activation of the thin actin-containing filaments in the sarcomere. R712L and M493I are mutations in the myosin amino acid sequence that cause hypertrophic cardiomyopathy. Their specific alterations in the mechanics and dynamics detectable in the optical trap help explain the etiology and effects of therapeutic interventions.