CAREER:3D nanosensors array for elucidating the electrical activity of induced pluripotent stem cells derived cardiomyocytes

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

PI: Cohen-Karni, Tzahi Proposal Number: 1552833 Stem cell derived neurons (brain cells) and cardiomyocytes (heart cells) are induced in a laboratory setting to create small scale cellular assemblies for various reasons, including therapeutic applications. It is desirable to monitor the development using methods so that we understand their functionality and their character. This project attempts to develop methods that will enable monitoring of the cells and cellular assemblies in three dimension. This is the first time attempts will be made to measure at a cellular level in cellular assemblies with high time resolution. The goal is to develop nanomaterials-based platforms for enabling measurement and understanding of electrical signals transduction within cellular assemblies, such as cardiac and brain tissue. In order to do so, the specific focus of the proposed work is on understanding signal propagation in 3D microscale cellular assemblies such as induced pluripotent stem cells derived neurons and cardiomyocytes (iPS-CM). In pursuit of this goal of using a 3D nanosensor array platform will enable the testing of the hypothesis that the development of electrical activity is correlated to the maturation of induced iPS-CMs. The approach will be to exploit both the bottom-up and top-down synthesis and assembly of nanomaterials to develop a 3D sensor array. This would enable electrophysiology studies of complex cellular assemblies and will shed light on electrophysiology related disease deficiencies such as Parkinson?s disease and cardiac arrhythmias by allowing multisite and scale intracellular measurements. The research is expected to provide high spatial-temporal resolution interfaces with cells, multiplexed communication, and complex materials assemblies that form the interfaces. Knowing how electrical information propagates in a tissue will provide an understanding of how signals are transduced in 3D cellular assemblies. This will shed light on the relationship between electrical signals and reported diseases such as arrhythmias, and Parkinson's disease, and will enable us to develop tools to amend either injured neurons or heart muscle tissue. It is planned to synthesize nanomaterials and design 3D nanosensors measurement platforms that will enable the first investigation into these processes. Specifically, research effort will focus on: (i) Defining the fundamental materials- properties to form the 3D organization of a nanosensor array. (ii) Investigating the interface between the nanosensors and the microscale cellular assembly and manipulating the interface, and (iii) Achieving multi-site electrical interfaces both intra-cellularly and extra-cellularly and determining the development and maturation of iPS-CM. The proposed research is the critical first step in measuring electrical activity in 3D. This novel measurement platform will potentially be transformative and will help us address broader challenges in such fields as stem cells, cardiomyocytes and neuronal cells electrical activity. The educational goal is to advance and promote teaching and research of nanosensing and nanoelectrical-biosensors at Carnegie Mellon University (CMU), especially for students majoring in engineering, and natural sciences programs. In pursuit of this goal, the educational objective is to use nanomaterials and nanosensing as tools in STEM education and spur grassroots innovation in bio-nanosensing. The educational approach is to (i) integrate the concepts of nanosensing into graduate and undergraduate class. (ii) teach and inspire high school juniors in underprivileged communities of greater Pittsburgh area, (iii) mentor undergraduate and graduate student in electrical nanosensing.