Electromechanical Interactions of Gold Nanomaterials with Human Cardiac Cells

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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.