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Emergent Global Contractile Force in Cardiac Tissues

Meghan B. Knight1, 3, Nancy K. Drew1, 3, 4, Linda A. McCarthy1, 3, Anna Grosberg1, 2, 3, 4, ,

1 Department of Biomedical Engineering, University of California-Irvine, Irvine, California

2 Department of Chemical and Biochemical Engineering and Materials Science, University of California-Irvine, Irvine, California

3 Center for Complex Biological Systems, University of California-Irvine, Irvine, California

4 The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California-Irvine, Irvine, California

Abstract

The heart is a complex organ whose structure and function are intricately linked at multiple length scales. Although several advancements have been achieved in the field of cardiac tissue engineering, current in vitro cardiac tissues do not fully replicate the structure or function necessary for effective cardiac therapy and cardiotoxicity studies. This is partially due to a deficiency in current understandings of cardiac tissue organization’s potential downstream effects, such as changes in gene expression levels. We developed a novel (to our knowledge) in vitro tool that can be used to decouple and quantify the contribution of organization and associated downstream effects to tissue function. To do so, cardiac tissue monolayers were designed into a parquet pattern to be organized anisotropically on a local scale, within a parquet tile, and with any desired organization on a global scale. We hypothesized that if the downstream effects were muted, the relationship between developed force and tissue organization could be modeled as a sum of force vectors. With the in vitro experimental platforms of parquet tissues and heart-on-a-chip devices, we were able to prove this hypothesis for both systolic and diastolic stresses. Thus, insight was gained into the relationship between the generated stress and global myofibril organization. Furthermore, it was demonstrated that the developed quantitative tool could be used to estimate the changes in stress production due to downstream effects decoupled from tissue architecture. This has the potential to elucidate properties coupled to tissue architecture, which change force production and pumping function in the diseased heart or stem cell-derived tissues.

… For contractility studies, coverslips were prepared as described by Grosberg et al. (21). Briefly, a large cover glass (Brain Research Laboratories, Newton, MA) was sonicated in 50% ethanol for 30 min. The cover glass …

Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved. Original Article

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