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Silicon Nanowires and Optical Stimulation for Investigations of Intra- and Intercellular Electrical Coupling

Myofibroblasts can spontaneously internalize silicon nanowires (SiNWs), making them an attractive target for bioelectronic applications. These ...

The University of Chicago

Electronic pacemakers can treat electrical conduction disorders in hearts; however, they are invasive, bulky, and linked to increased incidence of infection at the tissue-device interface. Thus, researchers have looked to other more biocompatible methods for cardiac pacing or resynchronization, such as femtosecond infrared light pulsing, optogenetics, and polymer-based cardiac patches integrated with metal electrodes. Here we develop a biocompatible nongenetic approach for the optical modulation of cardiac cells and tissues. We demonstrate that a polymer-silicon nanowire composite mesh can be used to convert fast moving, low-radiance optical inputs into stimulatory signals in target cardiac cells. Our method allows for the stimulation of the cultured cardiomyocytes or ex vivo heart to beat at a higher target frequency.

Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix.

The interface of biological components with semiconductors is a growing field with numerous applications. For example, the interfaces can be used to sense and modulate the electrical activity of single cells and tissues. From the materials point of view, silicon is the ideal option for such studies due to its controlled chemical synthesis, scalable lithography for functional devices, excellent electronic and optical properties, biocompatibility and biodegradability. Recent advances in this area are pushing the bio-interfaces from the tissue and organ level to the single cell and sub-cellular regimes. In this progress report, we will describe some fundamental studies focusing on miniaturizing the bioelectric and biomechanical interfaces. Additionally, many of our highlighted examples involve freestanding silicon-based nanoscale systems, in addition to substrate-bound structures or devices; the former offers new promise for basic research and clinical application. In this report, we will describe recent developments in the interfacing of neuronal and cardiac cells and their networks. Moreover, we will briefly discuss the incorporation of semiconductor nanostructures for interfacing non-excitable cells in applications such as probing intracellular force dynamics and drug delivery. Finally, we will suggest several directions for future exploration.

Talking to cells: semiconductor nanomaterials at the cellular interface.

Traditional bioelectronics, primarily comprised of nonliving synthetic materials, lack cellular behaviors such as adaptability and motility. This shortcoming results in mechanically invasive devices and nonnatural signal transduction across cells and tissues. Moreover, resolving heterocellular electrical communication in vivo is extremely limited due to the invasiveness of traditional interconnected electrical probes. In this paper, we present a cell-silicon hybrid that integrates native cellular behavior (e.g., gap junction formation and biosignal processing) with nongenetically enabled photosensitivity. This hybrid configuration allows interconnect-free cellular modulation with subcellular spatial resolution for bioelectric studies. Specifically, we hybridize cardiac myofibroblasts with silicon nanowires and use these engineered hybrids to synchronize the electrical activity of cardiomyocytes, studying heterocellular bioelectric coupling in vitro. Thereafter, we inject the engineered myofibroblasts into heart tissues and show their ability to seamlessly integrate into contractile tissues in vivo. Finally, we apply local photostimulation with high cell specificity to tackle a long-standing debate regarding the existence of myofibroblast-cardiomyocyte electrical coupling in vivo.

Living myofibroblast-silicon composites for probing electrical coupling in cardiac systems.

Current techniques for intracellular electrical interrogation are limited by substrate-bound devices, technically demanding methods, or insufficient spatial resolution. In this work, we use freestanding silicon nanowires to achieve photoelectric stimulation in myofibroblasts with subcellular resolution. We demonstrate that myofibroblasts spontaneously internalize silicon nanowires and subsequently remain viable and capable of mitosis. We then show that stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes in subcellular regions. Moreover, nanowire-myofibroblast hybrids electrically couple with cardiomyocytes in coculture, and photostimulation of the nanowires increases the spontaneous activation rate in coupled cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron-glia interactions using nanowire-containing oligodendrocytes.

Article	Year
Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 30538202	2019
Talking to cells: semiconductor nanomaterials at the cellular interface. Advanced biosystems\| PubMed ID: 30906852	2018
Living myofibroblast-silicon composites for probing electrical coupling in cardiac systems. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 31624124	2019
Silicon Nanowires for Intracellular Optical Interrogation with Subcellular Resolution. Nano letters\| PubMed ID: 31904975	2020

Menahem Y. Rotenberg

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