Subcellular interrogation of muscle dynamics with integrated optoelectronic arrays

对肌肉收缩和再生中钙信号的机制理解将受益于能够以亚细胞分辨率询问肌肉动力学的设备。本研究旨在为光电肌肉接口奠定基础，以精确调节和捕获肌肉中的钙动力学。这项研究的结果将产生新的肌肉接口工具和测定，这可以帮助更好地了解肌肉生理学的机制，并从长远来看提供一个可能的平台，以开发针对肌肉恢复的治疗方法。该提案的教育目标旨在培养和激励具有多学科背景的年轻工程师和科学家，以帮助确定再生医学，物理治疗和运动学的未来轨迹。该项目的更广泛的影响包括：1）推进变革性肌肉接口技术，以发展肌肉疗法; 2）教育代表性不足的本科生和研究生研究人员，为国家在生物技术和医疗保健方面的劳动力需求做出贡献; 3）在当地老年人和肌肉疾病支持团体中推广肌肉科学和技术。 本计画的研究目标是建立两个高密度的光电阵列，以亚细胞的精确度来询问肌肉收缩与再生过程的动力学。为了实现这一目标，这些阵列将采用可扩展的制造工艺来构建，以分别提供细胞内信号的双向光遗传学控制和芯片上荧光记录。从长远来看，两种阵列都可以沿着小腿结构构建，以最终提供进入深层肌肉组织的途径。本论文的学术价值将通过以下科学贡献得到证明：1）通过高密度光源阵列实现神经肌肉接头的亚细胞光遗传学调节; 2）通过高密度光电探测器阵列实现肌细胞中Ca ~（2+）和电压信号的亚细胞成像;和3）用两个光电阵列对肌肉收缩和再生过程进行亚细胞询问，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.