Myofibril remodeling of human stem cell-derived cardiomyocytes responding to dynamic surface topography

Statement of Purpose: Alignment of cardiomyocytes (CMs) has been recognized to be critical for maintaining in vivo-mimicking structures and physiological functions of the cardiac muscles. The alignment will induce anisotropic cell shape, and further organize the myofibril structures and contractile apparatuses for efficient contractile functions. To achieve CM alignment in vitro, nanoscale or submicron topographic features on the biomaterial substrates have been shown to promote the orientation and elongation of CMs, enhance the contractile functions, and increase formation of focal adhesion. Although it has been well documented that surface topography can strongly influence cell alignment and myofibril organization, it is less understood the dynamic cellular response of CMs to the topographic surface and remodeling process of myofibril architecture. To track cytoskeletal remodeling process of the myofibrils and sarcomeres occurring with cell alignment, we developed a dynamic programmable biomaterial substrate based on shape memory polymer (SMP), which can transit from flat surfaces to nano-wrinkled surfaces with the cells grown on the top. We derived the CMs from human induced pluripotent stem cells (hiPSC-CMs), and successfully cultured them with high cell viability on the SMP coated with polyelectrolyte multilayers (PEM). Using this system, we were be able to investigate the sequential reorganization of different myofibril components of hiPSC-CMs resulted from the nano-wrinkle formation.