Subcellular interrogation of muscle dynamics with integrated optoelectronic arrays

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Mechanistic understanding of calcium signaling in muscle contraction and regeneration will benefit from devices that can interrogate muscle dynamics at subcellular resolutions. This research project aims to lay the groundwork of optoelectronic muscle interfacing that can precisely modulate and capture the calcium dynamics in muscle. The outcome of this research will result in new muscle interfacing tools and assays, which can help better understand the mechanisms of muscle physiology, and in the long term offer a possible platform to develop therapeutics targeted to muscle recovery. The educational objectives of this proposal are aimed at training and inspiring young engineers and scientists with the multidisciplinary background required to help define the future trajectory of regenerative medicine, physical therapy, and kinesiology. The broader impacts of this project include: 1) advancing transformative muscle interfacing technologies towards the development of muscle therapeutics; 2) educating underrepresented undergraduate and graduate researchers to contribute to the nation’s workforce needs in biotechnology and healthcare, and 3) promoting muscle science and technology among local senior citizens and support groups for muscle diseases. The research objective of this proposal is to establish two high-density optoelectronic arrays to interrogate the dynamics of muscle contraction and regeneration processes at subcellular precision. To achieve this, these arrays will be built with scalable fabrication process to offer bi-directional optogenetic control and on-chip fluorescence recording of intracellular signals, respectively. In the long term, both arrays can be built along a shank structure to ultimately offer access to deep muscle tissue. The intellectual merit of the proposed work will be evidenced by the following scientific contributions: 1) subcellular optogenetic modulation of the neuromuscular junctions via a high-density light-source array; 2) subcellular imaging of the Ca2+ and voltage signals in muscle cells via a high-density photodetector array; and 3) subcellular interrogation of the muscle contraction and regeneration processes with two optoelectronic arrays, which will shed light on the development of muscle therapeutics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.