Simbios Talk by Ellen Kuhl, Stanford University, April 21, 2010

Title: A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis

Despite tremendous scientific progress during the past 20 years, heart failure remains one of the most common, costly, disabling, and deadly medical conditions affecting more than 25 million people worldwide. In hypertrophic cardiomyopathy, mechanical stimuli in the form of volume- and pressure-overload are believed to be the major driving forces for disease initiation and disease progression. In an attempt to better understand the pathologies of maladaptive cardiac growth, we seek to answer two fundamental questions: How do local changes in cellular morphology and cytoskeletal architecture translate into global alterations in cardiac form and function? and How are these changes regulated by mechanical factors? We present a novel computational model for maladaptive cardiac growth in which kinematic changes of the cardiac chambers are attributed to alterations in cytoskeletal architecture and in cellular morphology. We adopt the concept of finite volume growth characterized through the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. The functional form of its growth tensor is correlated to sarcomerogenesis, the creation and deposition of new sarcomere units. Using a generic bi-ventricular heart model subject to volume- and pressure-overload, we demonstrate how local changes in cellular morphology translate into global alterations in cardiac form and function.