Two photon optogenetic stimulation of human induced pluripotent stem cells derived cardiomyocytes

Control of cardiovascular tissue activity with light presents a non-contact alternative to electrical devices for cardiac pacing. The technique called optogenetics combines genetic modification with light-sensitive proteins such as Channelrhodopsin-2 (ChR2) and optical tools to perturb cellular activity. In this work, ChR2 was introduced into human induced pluripotent stem cells under the control of a ubiquitous promoter and respective cells were differentiated towards cardiomyocytes. Purified,light-sensitive cardiomyocytes were stimulated classically using blue light which has a limited tissue penetration depth for targeted stimulation. Thus, we demonstrate the use of a near-infrared femtosecond laser combined with beam shaping to stimulate arbitrary regions in a complex multi-cellular cardiac body. This high spatio-temporal technique may permit the stimulation of multiple cardiomyocytes and induce synchronous cardiac pacing with light.