Key result
Automated metrics for characterizing z-line architecture can quantitatively evaluate engineered tissues and elucidate mechanisms of force inefficiency in highly elongated cardiomyocytes.
Why the study?
Current methods to evaluate sarcomeric z-line architecture rely on manual or semi-manual image handling, leaving researchers without robust, repeatable tools to quantify how sarcomere structure impacts contraction.
Automated metrics for z-line architecture provide a robust, repeatable tool to quantitatively evaluate engineered striated muscle tissues.
Offers automated z-line analysis for preclinical engineered tissue studies; leaves open translation to clinical cardiac regeneration or force optimization.
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.
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Morris et al. (2020) studied Striated myocyte structural integrity. Automated analysis of sarcomeric z-discs vs. Manual or semi-manual methods was evaluated on Assessment of sarcomere order and z-line architecture. Automated metrics for characterizing z-line architecture can quantitatively evaluate engineered tissues and elucidate mechanisms of force inefficiency in highly elongated cardiomyocytes.
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