Speaker:  Tessa Moris, MCSB Ph.D. graduate student

Lab Affiliation: Dr. Anna Grosberg, Biomedical Engineering

Title: Assessing Continuous Z-line Length as a Metric for Cardiac Function

Abstract: The heart is organized into laminar sheets of cardiac fibers – myofibrils[1]. Furthermore, the structural remodeling of the myofibrils contributes to declined cardiac function in a diseased heart[2]. Within a myofibril, each sarcomere produces a contractile force parallel to the actin fibrils and ideally perpendicular to its z-lines, which are the boundaries between sarcomeres[3]. Because many sarcomeres work together to produce the force necessary for cardiac contractions, their spatial organization affects the heart’s ability to pump blood[4] . Therefore, measuring/quantifying precise sarcomere organization is an essential part of understanding the mechanisms that influence cardiac function. Based on qualitative experimental observations, it is hypothesized that cardiac tissues with sarcomeric z-lines that are registered between myofibrils tend to produce a greater contractile force. This hypothesis is supported by looking at single myofibrils in isolated cells[5]. Additionally, visibly shorter z-lines are considered a hallmark of immature stem-cell derived cardiac tissue. Based on these qualitative experimental observations, the degree of continuity and/or registration of sarcomeric z-lines is expected to correlate with cardiac force production that deviates from existing predictions. In this work, we measure the distance over which z-lines from multiple myofibrils are continuous, termed the continuous z-line length.  The continuous z-line length can be automatically and accurately measured from images of alpha-actinin stained cardiac tissue using the pixel and orientation information. The continuous z-line length has the potential to be used as a tool to better compare tissues and differentiation methods across labs and contribute a robust understanding of how tissue level structure affects the hearts mechanical function.

References

[1] Bursac, N., et al. Circulation research 91.12 (2002): e45-e54.

[2] Kim, Shokei, et al. Hypertension 25.6 (1995): 1252-1259.

[3] Ehler, Elisabeth, ed. Cardiac Cytoarchitecture: How to Maintain a Working Heart. Springer, 2015.

[4] Grosberg, Anna, et al.  Lab on a chip 11.24 (2011): 4165-4173.

[5]Friedrich, Benjamin M., et al. Biophysical journal 100.11 (2011): 2706-2715.

Acknowledgements

Edwards Lifesciences Center for Advanced Cardiovascular Technology’s NIH/NHLBI T32HL116270; NIH R01 HL129008 2015-2020; NSF DMS1763272 & Simons Foundation (594598, QN)