Stretch Harmonizes Sarcomere Strain Across the Cardiomyocyte

Li, Jia; Sundnes, Joakim; Hou, Yufeng; Laasmaa, Martin; Ruud, Marianne; Unger, Andreas; Kolstad, Terje R Selnes; Frisk, Michael; Norseng, Per Andreas; Yang, Limin; Setterberg, Ingunn E; Alves, Estela Santos; Kalakoutis, Michaeljohn; Sejersted, Ole M.; Lanner, Johanna T.; Linke, Wolfgang A.; Lunde, Ida G.; Tombe, Pieter P. de; Louch, William E.

doi:10.1161/circresaha.123.322588

Cited by 6 publications

(1 citation statement)

References 60 publications

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“…As a result, mechanical stimuli generated by cardiomyocytes can be recognized as mechanical stimuli. We postulated that dynamic cardiomyocyte culture at various stimulation levels would classify cardiac cell disease and physiology 42 , 43 . Cardiomyocytes were cultivated in the abovementioned chip with integrated in situ sensors and subjected to calibrated 5%, 10%, 15%, 20 and 25% cyclic stretch conditions for 24 h to confirm the notion mentioned above that cardiomyocytes respond to externally applied mechanical stimuli.…”

Section: Resultsmentioning

confidence: 99%

Strain sensor on a chip for quantifying the magnitudes of tensile stress on cells

Zhang,

Wang,

Yin

et al. 2024

Microsyst Nanoeng

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During cardiac development, mechanotransduction from the in vivo microenvironment modulates cardiomyocyte growth in terms of the number, area, and arrangement heterogeneity. However, the response of cells to different degrees of mechanical stimuli is unclear. Organ-on-a-chip, as a platform for investigating mechanical stress stimuli in cellular mimicry of the in vivo microenvironment, is limited by the lack of ability to accurately quantify externally induced stimuli. However, previous technology lacks the integration of external stimuli and feedback sensors in microfluidic platforms to obtain and apply precise amounts of external stimuli. Here, we designed a cell stretching platform with an in-situ sensor. The in-situ liquid metal sensors can accurately measure the mechanical stimulation caused by the deformation of the vacuum cavity exerted on cells. The platform was applied to human cardiomyocytes (AC16) under cyclic strain (5%, 10%, 15%, 20 and 25%), and we found that cyclic strain promoted cell growth induced the arrangement of cells on the membrane to gradually unify, and stabilized the cells at 15% amplitude, which was even more effective after 3 days of culture. The platform’s precise control and measurement of mechanical forces can be used to establish more accurate in vitro microenvironmental models for disease modeling and therapeutic research.

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Section: Resultsmentioning

confidence: 99%

Strain sensor on a chip for quantifying the magnitudes of tensile stress on cells

Zhang,

Wang,

Yin

et al. 2024

Microsyst Nanoeng

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Impact of stretch on sarcomere length variability in isolated fully relaxed rat cardiac myocytes

Lookin,

Boulali,

Cazorla

et al. 2023

Pflugers Arch - Eur J Physiol

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The contractility of cardiac muscle is greatly affected by preload via the Frank-Starling Mechanism (FSM). It is based on the preload-dependent activation of sarcomeres -the elementary contractile units in muscle cells. Recent ndings show a natural variability in sarcomere length (SL) in resting cardiomyocytes that, moreover, is altered in an actively contracting myocyte. SL variability may contribute to the FSM but it remains unresolved whether the change in the SL variability is regulated by activation process per se or simply by changes in cell stretch, i.e. average SL.To separate the roles of activation and SL, we characterized SL variability in isolated fully relaxed rat ventricular cardiomyocytes (n = 12) subjected to a longitudinal stretch with the carbon ber (CF) technique. Each cell was tested in three states: without CF attachment (control, no preload), with CF attachment without stretch, and with CF attachment and ~ 10% stretch of initial SL. The cells were imaged by transmitted light microscopy to retrieve and analyze individual SL and SL variability off-line by multiple quantitative measures like coe cient of variation or median absolute deviation.We found that CF attachment without stretch did not affect the extent of SL variability and averaged SL.In stretched myocytes, the averaged SL signi cantly increased while the SL variability remained unchanged. This result clearly indicates that the non-uniformity of individual SL is not sensitive to the average SL itself in fully relaxed myocytes. We conclude that SL variability per se does not contribute to the FSM in the heart.

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Electrophysiological tolerance: a new concept for understanding the electrical stability of the heart

Stokke,

Louch,

Smith

2024

Europace

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The coordinated electrical activity of ∼2 billion cardiac cells ensures stability of the heartbeat. Indeed, the remarkably low incidence (<1%) of ventricular arrhythmias in the healthy heart is only possible when the electrical event across this syncytium is closely controlled. In contrast, the diseased myocardium is associated with increased electrophysiological heterogeneity, unstable rhythm, and increased incidence of lethal arrhythmias. But what is the link between cellular and tissue level heterogeneity? Recent research has shown the existence of considerable cellular heterogeneity even in the healthy heart, suggesting that cell-to-cell variability in electrical (e.g. action potential duration) and mechanical performance (e.g. twitch amplitude) is a normal property. This observation has been previously unappreciated because the aggregated function in the form of QT-interval and cardiac output varies <1% on a beat-to-beat basis. This article describes the underlying cellular variability that is tolerated – and perhaps needed – by different regions of the heart for normal function and indicates why this variability is not apparent in function at the chamber and organ level. Thus, in contrast to the current dominant view, this article postulates that heterogeneity is normal and potentially endows various functional benefits. This new view of how the component parts of the heart come together to function also suggests novel mechanisms for cardiac pathologies, namely that dysfunction may emerge from changes in the extent and/or nature of heterogeneity. Once understood, restoring normal forms of heterogeneity could be a novel approach to treatment.

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Stretch Harmonizes Sarcomere Strain Across the Cardiomyocyte

Cited by 6 publications

References 60 publications

Strain sensor on a chip for quantifying the magnitudes of tensile stress on cells

Strain sensor on a chip for quantifying the magnitudes of tensile stress on cells

Impact of stretch on sarcomere length variability in isolated fully relaxed rat cardiac myocytes

Electrophysiological tolerance: a new concept for understanding the electrical stability of the heart

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