Coupling to substrate adhesions drives the maturation of muscle stress fibers into myofibrils within cardiomyocytes

Taneja, Nilay; Neininger, Abigail C.; Burnette, Dylan T.

doi:10.1091/mbc.e19-11-0652

Cited by 13 publications

(21 citation statements)

References 59 publications

(105 reference statements)

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“…Here, we show that the architecture needed for active force transmission across the length and width of the cardiomyocyte is already formed at birth, as a singular myofibrillar network spanning the entire cross-sectional diameter of the cell can be seen in the P1 cardiomyocytes (electronic supplementary material, video S2). While our earliest timepoint here was P1, it is likely that myofibrillar networks form in the heart before birth as evidence of significant sarcomere branching can be found in both embryonic cardiomyocytes [60] and in human-induced pluripotent stem cell-derived cardiomyocytes [61]. Moreover, similar to skeletal muscle cells [3], the connectivity of cardiac contractile networks is dynamic throughout postnatal development (figure 1), with sarcomere branching most frequent at P7, then decreasing at P14 and again at P42.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional remodelling of the cellular energy distribution system during postnatal heart development

Kim

Ajayi

Bleck

2022

Phil. Trans. R. Soc. B

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The heart meets the high energy demands of constant muscle contraction and calcium cycling primarily through the conversion of fatty acids into adenosine triphosphate (ATP) by a large volume of mitochondria. As such, the spatial relationships among lipid droplets (LDs), mitochondria, the sarcotubular system and the contractile apparatus are critical to the efficient distribution of energy within the cardiomyocyte. However, the connectivity among components of the cardiac cellular energy distribution system during postnatal development remains unclear. Here, we use volume electron microscopy to demonstrate that the sarcomere branches uniting the myofibrillar network occur more than twice as frequently during early postnatal development as in mature cardiomyocytes. Moreover, we show that the mitochondrial networks arranged in parallel to the contractile apparatus are composed of larger, more compact mitochondria with greater connectivity to adjacent mitochondria in mature as compared with early postnatal cardiomyocytes. Finally, we find that connectivity among mitochondria, LDs and the sarcotubular network is greater in developing than in mature muscles. These data suggest that physical connectivity among cellular structures may facilitate the communication needed to coordinate developmental processes within the cardiac muscle cell. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.

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Section: Discussionmentioning

confidence: 99%

Three-dimensional remodelling of the cellular energy distribution system during postnatal heart development

Kim

Ajayi

Bleck

2022

Phil. Trans. R. Soc. B

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“…Laser ablation is a widely used biophysical tool to assay the mechanical properties of cytoskeletal systems, such as stress fibers, epithelial cell–cell junctions and myofibrils (Fernandez‐Gonzalez, Simoes, Röper, Eaton, & Zallen, 2009; Lee et al, 2018; Roman et al, 2017; Taneja, Neininger, & Burnette, 2020). We have previously used this technique to interrogate cortex mechanics during cell division, as well as testing mechanical coupling between cell‐ECM adhesions and myofibrils (Taneja et al, 2020; Taneja, Neininger, & Burnette, 2020). Myofibrils are considered complex mechanical systems.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have implicated actin–titin interactions, collagen fibrils, and microtubule tyrosination as potential regulators of myofibril viscosity (Caporizzo et al, 2018; Granzier & Irving, 1995; Kulke et al, 2001). We have previously shown that FAK inhibition results in stabilization of cell‐ECM adhesions, which leads to increased incorporation of titin (Taneja, Neininger, & Burnette, 2020). Therefore, one possible mechanism could be due to increased actin–titin interactions mediated by increased cell‐ECM adhesion.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of this autophosphorylation using the inhibitor PF‐228 results in focal adhesion stabilization (Slack‐Davis et al, 2007; Taneja et al, 2016). Treatment of hiCMs with PF‐228 results in stabilization of focal adhesions, longer Z‐line lengths and increased incorporation of titin (Taneja, Neininger, & Burnette, 2020). However, the effect of focal adhesion stabilization by FAK on the mechanical properties of myofibrils remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Cardiomyocytes interact with the ECM at specialized sites called costameres, which anchor the Z-lines closest to the cell membrane to the ECM (Samarel, 2005). We have previously established a role for cell-ECM adhesion in myofibril assembly, using human iPSC-derived cardiomyocytes (hiCMs) as a model system (Taneja, Neininger, & Burnette, 2020). Cell-ECM sites transmit mechanical forces from immature myofibrils (muscle stress fibers) to the substrate, promoting their maturation.…”

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confidence: 99%

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Inhibition of focal adhesion kinase increases myofibril viscosity in cardiac myocytes

et al. 2020

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The coordinated generation of mechanical forces by cardiac myocytes is required for proper heart function. Myofibrils are the functional contractile units of force production within individual cardiac myocytes. At the molecular level, myosin motors form cross-bridges with actin filaments and use ATP to convert chemical energy into mechanical forces. The energetic efficiency of the cross-bridge cycle is influenced by the viscous damping of myofibril contraction. The viscoelastic response of myofibrils is an emergent property of their individual mechanical components. Previous studies have implicated titin-actin interactions, cell-ECM adhesion, and microtubules as regulators of the viscoelastic response of myofibrils. Here we probed the viscoelastic response of myofibrils using laser-assisted dissection. As a proof-of-concept, we found actomyosin contractility was required to endow myofibrils with their viscoelastic response, with blebbistatin treatment resulting in decreased myofibril tension and viscous damping. Focal adhesion kinase (FAK) is a key regulator of cell-ECM adhesion, microtubule stability, and myofibril assembly. We found inhibition of FAK signaling altered the viscoelastic properties of myofibrils. Specifically, inhibition of FAK resulted in increased viscous damping of myofibril retraction following laser ablation. This damping was not associated with acute changes in the electrophysiological properties of cardiac myocytes. These results implicate FAK as a regulator of mechanical properties of myofibrils.

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Hierarchical Topography with Tunable Micro‐ and Nanoarchitectonics for Highly Enhanced Cardiomyocyte Maturation via Multi‐Scale Mechanotransduction

Ahn

Cho

Yun

et al. 2023

Adv Healthcare Materials

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Enhancing cardiomyocyte (CM) maturation by topographical cues is a critical issue in cardiac tissue engineering. Thus far, single‐scale topographies with a broad range of feature shapes and dimensions have been utilized including grooves, pillars, and fibers. This study reports for the first time a hierarchical structure composed of nano‐pillars (nPs) on micro‐wrinkles (µWs) for effective maturation of CMs. Through capillary force lithography followed by a wrinkling process, vast size ranges of topographies are fabricated, and the responses of CMs are systematically investigated. Maturation of CMs on the hierarchical structures is highly enhanced compared to a single‐scale topography: cardiac differentiation of H9C2s (rat cardiomyocytes) on the hierarchical topography is ≈ 2.8 and ≈ 1.9 times higher than those consisting of single‐scale µWs and nPs. Both nPs and µWs have important roles in cardiac maturation, and the aspect ratio (height/diameter) of the nPs and the wavelength of the µWs are important in CM maturation. This enhancement is caused by strong focal adhesion and nucleus mediated mechanotransduction of CMs from the confinement effects of the different wavelengths of µWs and the cellular membrane protrusion on the nPs. This study demonstrates how a large family of hierarchical structures is used for cardiac maturation.

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Coupling to substrate adhesions drives the maturation of muscle stress fibers into myofibrils within cardiomyocytes

Cited by 13 publications

References 59 publications

Three-dimensional remodelling of the cellular energy distribution system during postnatal heart development

Three-dimensional remodelling of the cellular energy distribution system during postnatal heart development

Inhibition of focal adhesion kinase increases myofibril viscosity in cardiac myocytes

Hierarchical Topography with Tunable Micro‐ and Nanoarchitectonics for Highly Enhanced Cardiomyocyte Maturation via Multi‐Scale Mechanotransduction

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