Electromechanical Interactions of Gold Nanomaterials with Human Cardiac Cells

纳米材料在环境、生物工程和治疗等领域有着广泛的应用。在不同类型的纳米材料中，金纳米材料因其毒性小、易于制造和导电性好而成为有前途的候选材料。金纳米材料用于再生医学等应用，特别是用于可用于治疗创伤、损伤或疾病的导电组织（例如心脏、神经或骨骼）的工程。然而，关于金纳米材料与电活性人类心脏细胞之间相互作用的机制理解仍然存在知识空白。该研究团队在生物、环境和纳米技术工程方面具有跨学科的专业知识。该项目旨在合成不同几何形状的金纳米材料，并利用模拟多孔组织微环境的三维水凝胶生物材料，在细胞和分子水平上独立研究纳米材料与人类心脏细胞的生物物理和电相互作用。该项目经过精心设计，通过教育下一代高中生、本科生和研究生，对社会产生广泛影响，同时使跨学科领域的科学家之间产生协同作用。该项目的重点是开发一种机制和基本框架，用于研究金纳米材料与人类心脏细胞（即心脏细胞）的相互作用，从而调节它们的生物反应。研究设计基于双重策略，通过独立评估金纳米材料与心脏细胞的生物物理和电学相互作用。首先，一个具有广泛几何形状和明确表面化学性质的金纳米材料库将被合成，然后嵌入到基于水凝胶的支架生物材料中，以模拟心脏中发现的多孔原生组织微环境。随后，将在纳米水凝胶中评估金纳米材料的细胞摄取、表面定植、扩散以及心脏细胞骨架结构和特定蛋白质标记物的变化。接下来，将合成具有不同表面功能的金纳米颗粒，同时保持固定的颗粒几何形状，以特异性地分离纳米材料的不同电导率对心脏细胞电生理反应的影响。通过这些研究目标，研究小组将测试一个总体假设，即金纳米材料与心脏细胞的相互作用模式是通过两个主要的独立途径，金纳米材料通过这两个途径影响细胞水平的功能和分子水平的反应。这两种途径分别是生物物理和电生理传感。本研究的结果将为深入理解导电纳米材料与人体细胞的相互作用提供基础知识，并将进一步为生物和环境系统提供更好的纳米材料设计。此外，本研究的跨学科性质将培养下一代高中生、本科生和研究生，将广泛地向科学界展示本研究的方法和结果，并将跨学科领域的科学家和合作者聚集在一起，从生物工程到纳米技术、表面工程和细胞生物学。该奖项反映了美国国家科学基金会的法定使命，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。

Nanomaterials have been widely used for a diverse range of applications from environmental to biological engineering and therapeutics. Among different types of nanomaterials, gold nanomaterials are promising candidates because of their minimal toxicity, ease of fabrication, and electrical conductivity. Gold nanomaterials are used in applications such as regenerative medicine, specifically for engineering of electroconductive tissues (e.g. cardiac, nerve or skeletal) that could be used for treatment of trauma, injuries or diseases. However, there are still knowledge gaps regarding mechanistic understanding about interactions between gold nanomaterials with electroactive human heart cells. This research team brings interdisciplinary expertise in biological, environmental and nanotechnology engineering. It aims to synthesize diverse geometries of gold nanomaterials and use 3-dimensionsal hydrogel biomaterials that mimic a porous tissue microenvironment to independently study the biophysical and electrical interactions of nanomaterials with human heart cells at cellular and molecular levels. The project has been carefully designed to broadly impact society through educating the next generation of high school, undergraduate, and graduate students, while bringing synergy among scientists across interdisciplinary fields. This project focuses on the development of a mechanistic and fundamental framework for the interactions of gold nanomaterials with human cardiac cells (i.e. heart cells) that modulate their biological response. The research design is based on a two-fold strategy, through independent assessment of the biophysical and electrical interactions of gold nanomaterials with cardiac cells. First, a library of gold nanomaterials with a wide range of geometries and defined surface chemistries, will be synthesized and then embedded in hydrogel-based scaffolding biomaterials to mimic a porous native-like tissue microenvironment found in the heart. Subsequently, cellular uptake of gold nanomaterials, surface colonization, spreading as well as changes in cytoskeletal structure of the cardiac cells and specific protein markers will be assessed within the nano-enabled hydrogels. Next, gold nanoparticles will be synthesized with different surface functionalities, while maintaining a fixed particle geometry, to specifically isolate the effect of varying conductivity of nanomaterials on the electrophysiological response of cardiac cells. Through these research objectives, the team will test the overarching hypothesis that the mode of interaction of gold nanomaterials with cardiac cells is through two primary independent pathways by which gold nanomaterials influence the cellular-level function and molecular-level response of the cells. These two pathways are biophysical and electrophysiological sensing. The outcome of this study will generate fundamental knowledge for in depth understanding of interactions of conductive nanomaterials with human cells and will further enable better design of nanomaterials for biological and environmental systems. Additionally, the interdisciplinary nature of this study will train the next generation of high school, undergraduate and graduate students, will broadly present the methodology and the outcome of this research to the scientific community and will bring together scientist and collaborators across interdisciplinary fields, ranging from bioengineering to nanotechnology, surface engineering, and cell biology.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.