The Biophysics of Titin in Cardiac Health and Disease

Abstract

The giant protein titin is the third myofilament in the cardiac sarcomere. It is responsible for generating passive forces in stretched myocardium and maintaining sarcomere structure. The force generation properties of titin are determined by titin's elastic springlike elements, and this dissertation focuses on the determination of the physical properties of these springlike elements using atomic force microscopy. The primary project of this dissertation investigates the link between a single point mutation in one of titin's subdomains and arrhythmogenic cardiomyopathy.