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Background: The use of light to control the activity of living cells is a promising approach in cardiac research due to its unparalleled spatio-temporal selectivity and minimal invasiveness. Ziapin2, a newly synthesized azobenzene compound, has recently been reported as an efficient tool for light-driven modulation of excitation-contraction coupling (ECC) in human-induced pluripotent stem cells-derived cardiomyocytes. However, the exact biophysical mechanism of this process remains incompletely understood., Methods: To address this, we performed a detailed electrophysiological characterization in a more mature cardiac model, specifically adult mouse ventricular myocytes (AMVMs)., Results: Our in vitro results demonstrate that Ziapin2 can photomodulate cardiac ECC in mature AMVMs without affecting the main transporters and receptors located within the sarcolemma. We established a connection between Ziapin2-induced membrane thickness modulation and light-generated action potentials by showcasing the pivotal role of stretch-activated channels (SACs). Notably, our experimental findings, through pharmacological blockade, suggest that non-selective SACs might serve as the biological culprit responsible for the effect., Conclusions: Taken together, these findings elucidate the intricacies of Ziapin2-mediated photostimulation mechanism and open new perspectives for its application in cardiac research., Competing Interests: Declarations. Ethics approval and consent to participate: All experiments involving animals confirmed to the guidelines for Animal Care endorsed by the Milano-Bicocca and to the Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes. Consent for publication: Not applicable., (© 2024. The Author(s).)

The use of light for triggering skeletal and cardiac muscles allows lower invasiveness higher selectivity and unprecedented possibility to target individual cells or even subcellular compartments in a temporally and spatially precise manner. Because cells are in general transparent, this requires the development of suitable interfaces that bestow light sensitivity to living matter. In the present work, successfully demonstrated is the use of conjugated polymer films as transducer to optically enhance the contraction rate of a human and patient-specific cardiac in vitro cell model. By different experimental approaches, the coupling mechanism to the photothermal effect is assigned. This work extends the range of application of the polymer-mediated cell photostimulation phenomenon to cardiac muscle cells, opening up possible applications in cardiac therapy and for implementation of in vitro studies., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)