Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch

Abstract

An increase in mechanical load in the heart causes cardiac hypertrophy, either physiologically (heart development, exercise and pregnancy) or pathologically (high blood pressure and heart-valve regurgitation). Understanding cardiac hypertrophy is critical to comprehending the mechanisms of heart development and treatment of heart disease. However, the major molecular event that occurs during physiological or pathological hypertrophy is the dynamic process of sarcomeric addition, and it has not been observed. In this study, a custom-built second harmonic generation (SHG) confocal microscope was used to study dynamic sarcomeric addition in single neonatal CMs in a 3D culture system under acute, uniaxial, static, sustained stretch. Here we report, for the first time, live-cell observations of various modes of dynamic sarcomeric addition (and how these real-time images compare to static images from hypertrophic hearts reported in the literature): 1) Insertion in the mid-region or addition at the end of a myofibril; 2) Sequential addition with an existing myofibril as a template; and 3) Longitudinal splitting of an existing myofibril. The 3D cell culture system developed on a deformable substrate affixed to a stretcher and the SHG live-cell imaging technique are unique tools for real-time analysis of cultured models of hypertrophy.

Titin‐based mechanosensing modulates muscle hypertrophy

“…longitudinal hypertrophy 34, 35, 36. The current findings show that cyclic stretch of passive muscle is a strong stimulus for longitudinal growth of muscle fibres.…”

Heart Plasticity in Response to Pressure- and Volume-Overload: A Review of Findings in Compensated and Decompensated Phenotypes

“…Cardiac plasticity is a complex and multifactorial process. It is driven by mechanical load, the neurohormonal axis (Cohn et al, 2000;Yang et al, 2016), inflammation (Anzai, 2018), as well as autocrine and paracrine mediators (Gnecchi et al, 2008). Within the context of a whole organism these remodeling actors are interconnected and directly or indirectly influence one another.…”

Cofilin loss inDrosophilacontributes to myopathy through defective sarcomerogenesis and aggregate formation during muscle growth

“…This is particularly evident during the 2 nd to 3 rd instar transition, when control muscles experience the greatest rate of growth. TEM and live imaging data suggest that the ends of the myofibers are the sites of sarcomerogenesis (Dix and Eisenberg, 1990b;Yang et al, 2016). Further, the accumulation of F-actin at muscle cell poles has been previously observed in zebrafish models of NM (Sztal et al, 2015).…”

“…During this period, control muscles increased by 50% in both muscle cell length and sarcomere number, while a significant number of DmCFLknockdown muscles started accumulating F-actin at their poles ( Figure 2). The poles of muscle fibers have long been thought to be sites of sarcomerogenesis in both skeletal muscle fibers (Bai et al, 2007;Dix and Eisenberg, 1990a;HAAS, 1950), as well as cardiomyocytes (Yang et al, 2016). To determine whether DmCFL knockdown affects the addition of new sarcomeres during muscle cell growth, we specifically analyzed pairs of VL muscles in which one cell had a Class 1 (control-like) phenotype while the other was Class 2 (Figures 5A-5B).…”