UC Irvine

According to the World Health Organization (WHO) in year 2015 alone, 18 million people died from cardiovascular-related diseases, which makes for a staggering 31% of all global deaths. Recent studies of human cardiomyocytes in-vitro have been generating scientific insights beyond traditional approaches. However, in general, human cardiomyocytes are difficult to study due to limited sample availability and due to its fragile in-vitro nature. In this work, we studied HL-1 cells, a tumor-cell derived cardiomyocyte, to ultimately quantify the relationship between cell contractility and to investigate the influence of external stimuli. The motivation behind this study was to look into cardiomyocyte contractility as a quantifiable indicator for cardiotoxicity.

We first tried to understand the implications of biomechanical cues on cardiomyocyte orientation. HL-1 cells have the ability to grow in-vitro indefinitely while maintaining the ability to rhythmically contract autonomously upon reaching confluence. We found that HL-1 cells can mimic the characteristics of human cardiomyocyte, making them an excellent candidate for proof-of-concept demonstrations. They differ from human cardiomyocyte in that they lack a natural orientation and striation in-vitro. With the success of integrating substrates to incorporate nanoscale precision surface textures and which allow tissue engineering, the physiological environment of cells and tissues can be re-capitulated in-vitro. The purpose of this research was to align HL-1 cells on a polymer substrate to quantify their uniform contractility. We created an effective platform to observe cardiac contractility where the HL-1 cells are mechanically supported on a polymer substrate micro-machined with patterned grooves and ridges of nanoscale precision. Herein, we report on the quantitative efficiency of HL-1 cardiomyocyte alignment on various micro-patterned surfaces. The experimental results suggest that our micro-platform can promote cardiomyocyte alignment in-vitro, which is a crucial intermediate step towards rapid drug screening for cardiotoxicity.