TAM Seminar Series Presents:

Wendy C. Crone

Karen Thompson Medhi Professor of the College of Engineering

Discovery Fellow in the Wisconsin Institute for Discovery

University of Wisconsin-Madison

An Engineered Culture System for Human Cardiac Syncytium: Structural, Mechanical, and Electrical Readouts of Heart Cells in a Dish

Thursday, March 4th ? 10:00AM CST

Please log on with your Northwestern account (https://northwestern.zoom.us) to join.

Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as an exciting new tool for cardiac research and can serve as a pre-clinical platform for drug development and disease modeling studies. However, these aspirations are limited by current culture methods in which hPSC-CMs resemble fetal human cardiomyocytes in terms of structure and function. The Crone Lab has produced a novel platform for use with hPSC-CMs and human pluripotent stem cell-derived cardiac fibroblasts (hPSC-CFs), that includes patterned extracellular matrix (ECM) with physiological substrate stiffness to enhance these cells for in vitro studies. The platform is amenable to structural, mechanical, and electrical characterization.

When iPSC-CFs are confined to the micropatterned features of the platform they remodel the ECM into anisotropic fibers. Micropatterned lanes promote the cellular and myofibril alignment of hPSC-CMs while the addition of micropatterned bridges enable formation of a functional cardiac syncytium that beats synchronously over a large 2D area within the platform. Investigation of electrophysiological properties of the patterned cardiac constructs with optical mapping shows that they have anisotropic electrical impulse propagation, as occurs in the native myocardium. Interrogation of the mechanical function of the pattern constructs using digital image correlation (DIC) demonstrates the utility of this platform for mechanical characterization of coordinated contractions. Our results also show that iPSC-CFs influence iPSC-CM function with accelerated Ca2+ transient rise-up time and greater contractile strains in the co-culture conditions compared to when iPSC-CMs are cultured alone. Preliminary results will also be presented on the utility of this platform to investigate a hypertrophic cardiomyopathy (HCM) disease model.

Biography

Wendy C. Crone is the Karen Thompson Medhi Professor in the Department of Engineering Physics at the University of Wisconsin-Madison and is a Discovery Fellow with the Wisconsin Institute for Discovery. Her research is in the area of solid mechanics and is connected with biotechnology and nanotechnology. She has applied her technical expertise to improving fundamental understanding of mechanical response of materials, enhancing material behavior through surface modification and nanostructuring, exploring the interplay between cells and the mechanics of their surroundings, and developing new material applications and medical devices. Prof. Crone is a Fellow of the Society for Experimental Mechanics and has served in several leadership roles at UW-Madison, including prior appointments as Interim Dean and Associate Dean of the Graduate School.