Abstract
Cell-cell communication plays a pivotal role in biological systems' coordination and function. Electrical properties have been linked to specification and differentiation of stem cells into targeted progeny, such as neurons and cardiomyocytes. Currently, there is a critical need in developing new ways to complement fluorescent indicators, such as Ca2+-sensitive dyes, for direct electrophysiological measurements of cells and tissue. Here, we report a unique transparent and biocompatible graphene-based electrical platform that enables electrical and optical investigation of human embryonic stem cell-derived cardiomyocytes' (hESC-CMs) intracellular processes and intercellular communication. Graphene, a honeycomb sp2 hybridized two-dimensional carbon lattice, was synthesized using low pressure chemical vapor deposition system, and was tested for biocompatibility. Au and graphene microelectrode arrays (MEAs) were fabricated using well-established microfabrication methods. Au and graphene MEAs were interfaced with hESC-CMs to perform both optical and electrical recordings. Optical imaging and Raman spectroscopy confirmed the presence of monolayer graphene. Viability assay showed biocompatibility of graphene. Electrochemical characterization proved graphene's functional activity. Nitric acid treatment further enhanced the electrochemical properties of graphene. Graphene electrodes' transparency enabled both optical and electrical recordings from hESC-CMs. Graphene MEA detected changes in beating frequency and field potential duration upon β-adrenergic receptor agonist treatment. The transparent graphene platform enables the investigation of both intracellular and intercellular communication processes and will create new avenues for bidirectional communication (sensing and stimulation) with electrically active tissues and will set the ground for investigations reported diseases such as Alzheimer, Parkinson's disease and arrhythmias.
Highlights
Cell–cell communication plays a pivotal role in biological systems’ coordination and function
To further validate the recorded electrical signals and check if graphene microelectrode arrays (MEAs) platform can be used to detect changes in electrophysiology, the cells were treated with a standard drug, isoproterenol that stimulates the b-adrenergic receptors leading to an increase in beat frequency and a decrease in field potential duration (FPD).[17]
Fig-In conclusion, we demonstrated that the graphene electrodes enable simultaneous electrical and optical recordings from Human embryonic stem cells (hESCs)-CMs without affecting either of the recording modes
Summary
Cell–cell communication plays a pivotal role in biological systems’ coordination and function. Electrical properties have recently been linked to specification and differentiation of stem cells into targeted progeny such as neurons and cardiomyocytes.[3,30,44] Basic research at the tissue level of the heart and brain electrical activity has led to the development of tools to treat various ailments, such as pacemaker and deep brain stimulation electrodes.[9,12] Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)-derived cardiomyocytes (CMs) provide a promising tool to study cardiac developmental biology, regenerative therapies, disease modeling, and drug discovery.[20,23,33,36,46] These cells represent human-like physiology and have the potential to self-renew indefinitely are advantageous over the traditional cells and ex vivo models obtained from animals.[23,46] Electrophysiology is a powerful tool to study the maturity of CMs, their functional properties, effect of therapeutics on cellular physiology, and intercellular communication.[5,22,33]
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