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Numerous diseases, including those of the heart, are characterized by increased stiffness due to excessive deposition of extracellular matrix proteins. Cardiomyocytes continuously adapt their morphology and function to the mechanical changes of their microenvironment. Because traditional cell culture is conducted on substrates that are many orders of magnitude stiffer than any environment encountered by a cardiomyocyte in health or disease, alternate culture systems are necessary to model these processes in vitro. Here, we employ photo-clickable thiol-ene poly(ethylene glycol) (PEG) hydrogels for three-dimensional cell culture of adult mouse cardiomyocytes. PEG hydrogels serve as versatile biocompatible scaffolds, whose stiffness can be precisely tuned to mimic physiological and pathological microenvironments. Compared to traditional culture, adult cardiomyocytes encapsulated in PEG hydrogels exhibited longer survival and preserved sarcomeric and T-tubular architecture. Culture in PEG hydrogels of varying stiffnesses regulated the subcellular localization of the mechanosensitive transcription factor, YAP, in adult cardiomyocytes, indicating PEG hydrogels offer a versatile platform to study the role of mechanical cues in cardiomyocyte biology., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Optogenetics provides a tool for controlling the electrical activity of excitable cells by means of the interaction of light with light-gated ion channels. Despite the fact that optogenetics has been intensively utilized in the neurosciences, it has been more rarely employed as an instrument for studying cardiac pathophysiology. However, the advantages of optical approaches to perturb cardiac electrical activity are numerous, especially when the spatio-temporal qualities of light are utterly exploited. Here, we review the main breakthroughs employing optogenetics to perturb cardiac pathophysiology and attempt a comparison of methods and procedures that have employed optogenetics in the heart. We particularly focus on light-based defibrillation strategies that represent one of the latest achievements in this field. We highlight the important role of advanced optical methods for detecting and stimulating electrical activity for optimizing defibrillation strategies and, more generally, for dissecting novel insights in cardiac physiology. Finally, we discuss the main future perspectives that we envision for optogenetics in the heart, both in terms of translational applications and for addressing fundamental questions of cardiac function., (Copyright © 2017 Elsevier Ltd. All rights reserved.)