Fundamental Investigations of Muscle Cell Interactions for Engineering 'Living Diodes'

PI：ZorluTuna，Pina提案编号：1403546机构：康涅狄格大学题目：工程‘活二极管’的肌肉细胞相互作用基础研究生物计算是一个新兴的领域，旨在使用生物组件进行信号处理。肌肉细胞既有电响应，又有机械响应，很有希望成为这种新的信息处理方法的候选者。使用基于肌肉细胞的活体机电电路元件实现可控和可靠的定向信号流可以改变生物电学和生物力学接口的设计方式，并影响基础科学和生物工程应用。这项拟议的研究将导致对肌肉细胞网络中细胞-细胞和细胞-环境交流的更好理解，影响未来潜在的应用，从生物机器人学和人机界面到理解和治疗肌肉退行性疾病和心律失常的生物工程方法。这样的进步将解决重要的社会问题，如肢体丧失和心脏病。除了与这项研究相关的专业出版物和拟议的联合组织的会议研讨会外，还计划为大学、高中和中学的学生和教师开展教育和推广活动。这个奖项是由两个节目联合颁发的。(1)生物医学工程，在化学、生物工程、环境和运输系统部(工程局)；(2)生物研究仪器开发，在生物基础设施部(生物科学局)。这个项目的目标是检测一种新型二极管的特性，这种二极管由可兴奋的肌肉细胞和不可兴奋的成纤维细胞的新组合制成，然后研究这些细胞类型之间更复杂的相互作用，这些细胞被组织起来作为逻辑门，最终作为机电电路。为了实现这一目标，该提议测试了特定的假设，即这两种细胞类型的非均匀排列可以被设计为允许信号在可兴奋到不可兴奋方向上传播，但不能反向传播。第一个研究目标是利用独特组合的微电极阵列、三维荧光和原子力显微镜研究微图案化肌肉细胞的二极管样行为，使用单细胞机械和单细胞电刺激，以电、光/化学和机械方式对限定的几何形状的单个细胞或细胞群进行询问。第二个研究目标是研究各种微图案化的几何结构和可激发/不可激发细胞组合的比率，以研究信号传播的基本特性，明确的目标是最终设计逻辑门类似物。这项拟议的研究将为开辟一个新的领域铺平道路，在这个领域，基于肌肉细胞的结构可以用作电路元件，随后作为生物电学和生物力学接口，并作为人工生物系统的控制单元，具有明显的生物计算应用和人机接口的潜在机会。

PI: Zorlutuna, Pinar Proposal Number: 1403546Institution: University of ConnecticutTitle: Fundamental Investigations of Muscle Cell Interactions for Engineering 'Living Diodes'Biocomputing is an emerging field that aims to use biological components for signal processing. Muscle cells, being both electrically and mechanically responsive, are promising candidates for this new approach to information processing. Achieving controlled and reliable directional signal flow using muscle cell-based living electromechanical circuit elements can transform how bioelectrical and biomechanical interfaces are engineered, and impact both fundamental science and bioengineering applications. The proposed research will lead to a better understanding of cell-cell and cell-environment communication in muscle cell networks, impacting potential future applications ranging from biorobotics and human-machine interfaces to bioengineering approaches for understanding and treating muscular degenerative disorders and cardiac arrhythmia. Such advancements will address socially important problems, such as limb loss and heart diseases. Beyond professional publications and a proposed co-organized conference symposium related to this research, educational and outreach activities are planned for university, high school, and middle school students and teachers. This award is being made jointly by two Programs. (1) Biomedical Engineering, in the Chemical, Bioengineering, Environmental and Transport Systems Division (Engineering Directorate); and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).The goal of this project is to examine the properties of a new type of diode, made from a novel combination of excitable muscle cells and non-excitable fibroblast cells, and then study more complex interactions between these cell types that are organized to function as logic gates and eventually as electromechanical circuits. To achieve this goal, this proposal tests the specific hypothesis that a non-uniform arrangement of these two cell types can be engineered to allow signal propagation in the excitable to non-excitable direction, but not the reverse. The first research objective is to study diode-like behavior of micropatterned muscle cells using single-cell mechanical and single-cell electrical stimulation with uniquely combined microelectrode arrays, 3-dimensional fluorescence, and atomic force microscopy for electrical, optical/chemical, and mechanical interrogation of individual cells, or populations of cells, confined to defined geometries. The second research objective is to study various micropatterned geometries and ratios of excitable/non-excitable cell combinations to investigate the fundamental properties of the signal propagation, with the explicit goal of ultimately engineering logical gate analogues. The proposed research will pave the way for opening up a new field in which muscle cell-based structures can be used as circuit elements that subsequently serve as bioelectrical and biomechanical interfaces, and as control units for artificial bio-systems with clear potential opportunities for biocomputing applications and human/machine interfaces.