Striated myocyte structural integrity: Automated analysis of sarcomeric z-discs.

Autor: Morris TA; Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.; Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, California, United States of America., Naik J; Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, California, United States of America.; Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, California, United States of America., Fibben KS; Department of Biomedical Engineering, University of California, Irvine, Irvine, California, United States of America., Kong X; Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, United States of America., Kiyono T; Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan., Yokomori K; Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, United States of America., Grosberg A; Center for Complex Biological Systems, University of California, Irvine, Irvine, California, United States of America.; Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, California, United States of America.; Department of Chemical and Biomolecular Engineering, University of California, Irvine, Irvine, California, United States of America.; Department of Biomedical Engineering, University of California, Irvine, Irvine, California, United States of America.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2020 Mar 04; Vol. 16 (3), pp. e1007676. Date of Electronic Publication: 2020 Mar 04 (Print Publication: 2020).
DOI: 10.1371/journal.pcbi.1007676
Abstrakt: As sarcomeres produce the force necessary for contraction, assessment of sarcomere order is paramount in evaluation of cardiac and skeletal myocytes. The uniaxial force produced by sarcomeres is ideally perpendicular to their z-lines, which couple parallel myofibrils and give cardiac and skeletal myocytes their distinct striated appearance. Accordingly, sarcomere structure is often evaluated by staining for z-line proteins such as α-actinin. However, due to limitations of current analysis methods, which require manual or semi-manual handling of images, the mechanism by which sarcomere and by extension z-line architecture can impact contraction and which characteristics of z-line architecture should be used to assess striated myocytes has not been fully explored. Challenges such as isolating z-lines from regions of off-target staining that occur along immature stress fibers and cell boundaries and choosing metrics to summarize overall z-line architecture have gone largely unaddressed in previous work. While an expert can qualitatively appraise tissues, these challenges leave researchers without robust, repeatable tools to assess z-line architecture across different labs and experiments. Additionally, the criteria used by experts to evaluate sarcomeric architecture have not been well-defined. We address these challenges by providing metrics that summarize different aspects of z-line architecture that correspond to expert tissue quality assessment and demonstrate their efficacy through an examination of engineered tissues and single cells. In doing so, we have elucidated a mechanism by which highly elongated cardiomyocytes become inefficient at producing force. Unlike previous manual or semi-manual methods, characterization of z-line architecture using the metrics discussed and implemented in this work can quantitatively evaluate engineered tissues and contribute to a robust understanding of the development and mechanics of striated muscles.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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