Date of Graduation


Document Type


Degree Type



School of Medicine


Physiology, Pharmacology & Neuroscience

Committee Chair

Robert Wysolmerski


Myosins are molecular motors that convert chemical energy into mechanical force. Vertebrate cells contain three myosin II isoforms, designated as myosin IIA, IIB and IIC, and each isoform has unique biochemical and biophysical charasterics. It is generally accepted that all three isoforms are involved in regulating actin structures and cell contraction. However, it is unknown what role(s) each isoform plays in maintaining actin structures and generating cellular force. Experiments presented in this thesis will begin to document what role myosin IIA plays in endothelial cell contraction and actin dynamics.;Myosin IIA ablated from endothelial cells by infection with adenovirus encoding a short hairpin interfering RNA targeting mouse nonmuscle myosin IIA (shRNAi-IIA) mediated knockdown of myosin IIA, altered endothelial cell shape and induced reorganization of actin filaments. Myosin IIB content was unaltered and myosin IIB remained associated with actin filaments. Cell attachement and spreading occured faster and there was an increase in cell motility compared to control cultures. Loss of myosin IIA resulted in a 40% reduction in basal force production and a significantly blunted thrombin induced cell contraction. These results show myosin IIA is needed for normal endothelial cell functions and is essential for generation of basal and agonist-induced force.