Megan Hammell

M. Biomedical Engineering (candidate)

Project : Smooth muscle mechanics in the latch-state

Smooth muscle is found in all hollow organs of the body. Phasic muscle (e.g. in intestine) serves to propel content whereas tonic muscle (e.g. in blood vessels) maintains tone. Tonic smooth muscle is unique in its ability to maintain force for long periods of time at low energy (ATP) cost. This characteristic is called the latch-state and was first described as a property of the myosin molecular motor solely. Myosin is composed of two heavy chains, two regulatory light chains (LC20) and two essential light chains. Smooth muscle myosin is activated through the phosphorylation of LC20 by a Ca2+-calmodulin dependent myosin light chain kinase (MLCK). Once phosphorylated, smooth muscle myosin hydrolyzes ATP into ADP and Pi, then attaches to actin and generates force and motion through the release of Pi and ADP. It is believed that the latch state occurs when the LC20 gets deactivated (dephosphorylated) while myosin is still attached to actin.

Megan’s hypothesis is that the latch state can be reproduced at the molecular level by LC20 dephosphorylation while myosin is interacting with actin. Thus, Megan will use an optical trap to measure the force generated by a population of myosin molecules on an actin filament during LC20 dephosphorylation.