Dynamic control of contractile resistance to iPSC-derived micro-heart muscle arrays.

Abstract

Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, our understanding of how mechanical forces exactly affect the cellular biology of the heart remains incomplete. In vitro models based on cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CM) enable researchers to develop medium to high-throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces, such as cardiac afterload. However, most of these models require exogenous extracellular matrix (ECM) to form cardiac tissues. Recently, a system was developed to simulate changes in afterload by grafting ECM-free micro-heart muscle arrays to elastomeric substrates of discrete stiffnesses. In the present study, we extended this system by combining the elastomer-grafted tissue arrays with a magnetorheological elastomeric substrate. This system allows iPSC-CM based micro-heart muscle arrays to experience dynamic changes in contractile resistance to mimic dynamically altered afterload. Acute changes in substrate stiffness led to acute changes in the calcium dynamics and contractile forces, illustrating the system's ability to dynamically elicit changes in tissue mechanics by dynamically changing contractile resistance.