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Molecular-scale visualization of sarcomere contraction within native cardiomyocytes.

ABSTRACT: Sarcomeres, the basic contractile units of striated muscle, produce the forces driving muscular contraction through cross-bridge interactions between actin-containing thin filaments and myosin II-based thick filaments. Until now, direct visualization of the molecular architecture underlying sarcomere contractility has remained elusive. Here, we use in situ cryo-electron tomography to unveil sarcomere contraction in frozen-hydrated neonatal rat cardiomyocytes. We show that the hexagonal lattice of the thick filaments is already established at the neonatal stage, with an excess of thin filaments outside the trigonal positions. Structural assessment of actin polarity by subtomogram averaging reveals that thin filaments in the fully activated state form overlapping arrays of opposite polarity in the center of the sarcomere. Our approach provides direct evidence for thin filament sliding during muscle contraction and may serve as a basis for structural understanding of thin filament activation and actomyosin interactions inside unperturbed cellular environments.

SUBMITTER: Burbaum L

PROVIDER: S-EPMC8253822 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Molecular-scale visualization of sarcomere contraction within native cardiomyocytes.

Burbaum Laura L Schneider Jonathan J Scholze Sarah S Böttcher Ralph T RT Baumeister Wolfgang W Schwille Petra P Plitzko Jürgen M JM Jasnin Marion M

Nature communications 20210702 1

Sarcomeres, the basic contractile units of striated muscle, produce the forces driving muscular contraction through cross-bridge interactions between actin-containing thin filaments and myosin II-based thick filaments. Until now, direct visualization of the molecular architecture underlying sarcomere contractility has remained elusive. Here, we use in situ cryo-electron tomography to unveil sarcomere contraction in frozen-hydrated neonatal rat cardiomyocytes. We show that the hexagonal lattice o ...[more]

PMID: 34215727

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Project description:Cardiomyocytes contract keeping their sarcomere length (SL) close to optimal values for force generation. Transmural heterogeneity in SL across the ventricular wall coordinates the contractility of the whole-ventricle. SL heterogeneity (variability) exists not only at the tissue (macroscale) level, but also presents at the level of a single cardiomyocyte (microscale level). However, transmural differences in intracellular SL variability and its possible dependence on the state of contraction (e.g. end-diastole or end-systole) have not been previously reported. In the present study, we studied three aspects of sarcomere-to-sarcomere variability in intact cardiomyocytes isolated from the left ventricle of healthy guinea-pig: 1) transmural differences in SL distribution between subepi- (EPI) and subendocardial (ENDO) cardiomyocytes; 2) the dependence of intracellular variability in SL upon the state of contraction; 3) local differences in SL variability, comparing SL distributions between central and peripheral regions within the cardiomyocyte. To characterize the intracellular variability of SL, we used different normality tests for the assessment of SL distributions, as well as nonparametric coefficients to quantify the variability. We found that individual SL values in the end-systolic state of contraction followed a normal distribution to a lesser extent as compared to the end-diastolic state of contraction (∼1.3-fold and ∼1.6-fold in ENDO and EPI, respectively). The relative and absolute coefficients of sarcomere-to-sarcomere variability in end-systolic SL were significantly greater (∼1.3-fold) as compared to end-diastolic SL. This was independent of both the transmural region across the left ventricle and the intracellular region within the cardiomyocyte. We conclude that the intracellular variability in SL, which exists in normal intact guinea-pig cardiomyocytes, is affected by the contractile state of the myocyte. This phenomenon may play a role in inter-sarcomere communication in the beating heart.

Dataset Information

Molecular-scale visualization of sarcomere contraction within native cardiomyocytes.

Publications

Molecular-scale visualization of sarcomere contraction within native cardiomyocytes.

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