Revealing how heart cells detect stretch

The caveolar coat complex as a mediator of mechano-sensation in the heart

The ability of heart cells to sense stretching is essential for normal heart function, and allows the heart to pump more blood when it is needed, like during exercise. When cells are stretched too much and too often, the heart can change and develop heart failure and abnormal heart rhythms. Understanding how the heart senses stretch and how this leads to changes in the structure of the heart is important to understanding how heart failure develops. Recently, a new type of movement ‘sensor’ has emerged. Caveolae are tiny folds in the outer wall of cells, made up of proteins called caveolins and cavins. These proteins come together to make up a protein complex called the ‘caveolar coat complex’ (CCC). In this project, Dr Calaghan and her team will explore how this protein complex detects the level of stretch and movement in heart cells, and what it does in response to these changes. By studying heart cells isolated from rats, she will determine the exact make up of the CCC. Using imaging techniques that can zoom to single-molecule level, she will assess the shape of the caveolae and the organisation of caveolin and cavin proteins within the complex, and see how they respond to changes in stretch. The findings will hopefully bring us closer to understanding how heart failure develops.