An amphiphilic plasma membrane-targeted photo-transducer mediates optical pacing in cardiomyocytes derived from human induced pluripotent stem cells.

Abstract

The use of light to control the activity of different cell-types has recently come at the forefront of the scientific community thanks to a series of key-enabling characteristics (i.e. spatial/temporal selectivity, and lower invasiveness). Notably, non-genetic photostimulation is a novel and rapidly growing multidisciplinary field of research that aims to induce light sensitivity in living systems by exploiting exogeneous phototransducers. Here we propose a recently synthetized actuator, based on an azobenzene derivative, for cardiac applications. The light-mediated photostimulation process has been studied by applying several characterization techniques to detect the effect on the cellular properties of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In particular, we recorded changes in membrane capacitance, in membrane potential (Vm), intracellular Ca2+ dynamics and cell contractility. Light stimulation of the photo-transducers causes a transient Vm hyperpolarization followed by a delayed depolarization and action potential (AP) generation. The observed increase in AP frequency nicely correlates with changes in Ca2+ dynamics and contraction rate. Altogether, these preliminrary evidences provide the proof of concept that our amphiphilic plasma membrane-targeted photo-transducer is a viable tool to modulate electrical activity and contractility in hiPSC-CMs, opening up a broader field of applications in cardiac electrophysiology.