Atomic force spectroscopy is a promising tool to study contractile properties of cardiac cells

Kabanov, Daniil; Klimovič, Šimon; Rotrekl, Vladimír; Pešl, Martin; Přibyl, Jan

doi:10.1016/j.micron.2021.103199

Cited by 6 publications

(3 citation statements)

References 99 publications

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“…Furthermore, EV-H5 significantly improved the functional properties of CMs. To demonstrate this, we used AFM-based spectroscopy and fluorescence microscopy, techniques whose application in cardiac research has not yet been fully recognized [ 64 ]. By measuring contractile parameters of CMs at the single cell level, we provide direct evidence of sustained contractility and calcium handling after EV-H5 treatment (Fig.…”

Section: Discussionmentioning

confidence: 99%

Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling

Bobis-Wozowicz,

Paw,

Sarna

et al. 2024

Cell Commun Signal

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Background Stem cell-derived extracellular vesicles (EVs) are an emerging class of therapeutics with excellent biocompatibility, bioactivity and pro-regenerative capacity. One of the potential targets for EV-based medicines are cardiovascular diseases (CVD). In this work we used EVs derived from human induced pluripotent stem cells (hiPSCs; hiPS-EVs) cultured under different oxygen concentrations (21, 5 and 3% O2) to dissect the molecular mechanisms responsible for cardioprotection. Methods EVs were isolated by ultrafiltration combined with size exclusion chromatography (UF + SEC), followed by characterization by nanoparticle tracking analysis, atomic force microscopy (AFM) and Western blot methods. Liquid chromatography and tandem mass spectrometry coupled with bioinformatic analyses were used to identify differentially enriched proteins in various oxygen conditions. We directly compared the cardioprotective effects of these EVs in an oxygen-glucose deprivation/reoxygenation (OGD/R) model of cardiomyocyte (CM) injury. Using advanced molecular biology, fluorescence microscopy, atomic force spectroscopy and bioinformatics techniques, we investigated intracellular signaling pathways involved in the regulation of cell survival, apoptosis and antioxidant response. The direct effect of EVs on NRF2-regulated signaling was evaluated in CMs following NRF2 inhibition with ML385. Results We demonstrate that hiPS-EVs derived from physiological hypoxia at 5% O2 (EV-H5) exert enhanced cytoprotective function towards damaged CMs compared to EVs derived from other tested oxygen conditions (normoxia; EV-N and hypoxia 3% O2; EV-H3). This resulted from higher phosphorylation rates of Akt kinase in the recipient cells after transfer, modulation of AMPK activity and reduced apoptosis. Furthermore, we provide direct evidence for improved calcium signaling and sustained contractility in CMs treated with EV-H5 using AFM measurements. Mechanistically, our mass spectrometry and bioinformatics analyses revealed differentially enriched proteins in EV-H5 associated with the antioxidant pathway regulated by NRF2. In this regard, EV-H5 increased the nuclear translocation of NRF2 protein and enhanced its transcription in CMs upon OGD/R. In contrast, inhibition of NRF2 with ML385 abolished the protective effect of EVs on CMs. Conclusions In this work, we demonstrate a superior cardioprotective function of EV-H5 compared to EV-N and EV-H3. Such EVs were most effective in restoring redox balance in stressed CMs, preserving their contractile function and preventing cell death. Our data support the potential use of hiPS-EVs derived from physiological hypoxia, as cell-free therapeutics with regenerative properties for the treatment of cardiac diseases.

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Section: Discussionmentioning

confidence: 99%

Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling

Bobis-Wozowicz,

Paw,

Sarna

et al. 2024

Cell Commun Signal

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“…The measurement of cardiac contractility could be performed on different levels, from single cardiomyocytes to whole organs. For example, atomic force microscopy (AFM) has been applied to detect the beat rate and beat force of a single cardiomyocyte [ 107 ]. Ultrasound Cardiogram (UCG) has been used to measure the ejection fraction of a living heart [ 108 ].…”

Section: Interpreting Tissue-specific Functionalities From Different ...mentioning

confidence: 99%

Heart-on-a-chip systems with tissue-specific functionalities for physiological, pathological, and pharmacological studies

Gu,

Han,

Cao

et al. 2024

Materials Today Bio

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“…Most CVD involves changes in the morphological and mechanical properties of cells, such as red blood cells, cardiomyocytes, smooth muscle cells, etc. (Borin et al, 2018; Kabanov et al, 2022; Lekka et al, 2005; Loyola‐Leyva et al, 2018; Sun et al, 2005). Also involved in tissue stiffness due to changes in ECM composition (Benech & Romanelli, 2022).…”

Section: Cardiovascular and Cerebrovascular Diseasesmentioning

confidence: 99%

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Liu,

Han,

Kong

et al. 2023

Microscopy Res & Technique

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Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that “force” represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM.Research HighlightsBy examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.

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Atomic force spectroscopy is a promising tool to study contractile properties of cardiac cells

Cited by 6 publications

References 99 publications

Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling

Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling

Heart-on-a-chip systems with tissue-specific functionalities for physiological, pathological, and pharmacological studies

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

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