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Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes

A highly organized cytoskeleton architecture is the basis for continuous and controlled contraction in cardiomyocytes (CMs). Abnormalities in cytoskeletal elements, like the Z-disc, are linked to several diseases. It is challenging to reveal the mechanisms of CM failure, endogenous repair, or mechan...

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Autores principales: Müller, Dominik, Hagenah, Dorian, Biswanath, Santoshi, Coffee, Michelle, Kampmann, Andreas, Zweigerdt, Robert, Heisterkamp, Alexander, Kalies, Stefan M. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403391/
https://www.ncbi.nlm.nih.gov/pubmed/30842507
http://dx.doi.org/10.1038/s41598-019-40308-z
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author Müller, Dominik
Hagenah, Dorian
Biswanath, Santoshi
Coffee, Michelle
Kampmann, Andreas
Zweigerdt, Robert
Heisterkamp, Alexander
Kalies, Stefan M. K.
author_facet Müller, Dominik
Hagenah, Dorian
Biswanath, Santoshi
Coffee, Michelle
Kampmann, Andreas
Zweigerdt, Robert
Heisterkamp, Alexander
Kalies, Stefan M. K.
author_sort Müller, Dominik
collection PubMed
description A highly organized cytoskeleton architecture is the basis for continuous and controlled contraction in cardiomyocytes (CMs). Abnormalities in cytoskeletal elements, like the Z-disc, are linked to several diseases. It is challenging to reveal the mechanisms of CM failure, endogenous repair, or mechanical homeostasis on the scale of single cytoskeletal elements. Here, we used a femtosecond (fs) laser to ablate single Z-discs in human pluripotent stem cells (hPSC) -derived CMs (hPSC-CM) and neonatal rat CMs. We show, that CM viability was unaffected by the loss of a single Z-disc. Furthermore, more than 40% of neonatal rat and 68% of hPSC-CMs recovered the Z-disc loss within 24 h. Significant differences to control cells, after the Z-disc loss, in terms of cell perimeter, x- and y-expansion and calcium homeostasis were not found. Only 14 days in vitro old hPSC-CMs reacted with a significant decrease in cell area, x- and y-expansion 24 h past nanosurgery. This demonstrates that CMs can compensate the loss of a single Z-disc and recover a regular sarcomeric pattern during spontaneous contraction. It also highlights the significant potential of fs laser-based nanosurgery to physically micro manipulate CMs to investigate cytoskeletal functions and organization of single elements.
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spelling pubmed-64033912019-03-11 Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes Müller, Dominik Hagenah, Dorian Biswanath, Santoshi Coffee, Michelle Kampmann, Andreas Zweigerdt, Robert Heisterkamp, Alexander Kalies, Stefan M. K. Sci Rep Article A highly organized cytoskeleton architecture is the basis for continuous and controlled contraction in cardiomyocytes (CMs). Abnormalities in cytoskeletal elements, like the Z-disc, are linked to several diseases. It is challenging to reveal the mechanisms of CM failure, endogenous repair, or mechanical homeostasis on the scale of single cytoskeletal elements. Here, we used a femtosecond (fs) laser to ablate single Z-discs in human pluripotent stem cells (hPSC) -derived CMs (hPSC-CM) and neonatal rat CMs. We show, that CM viability was unaffected by the loss of a single Z-disc. Furthermore, more than 40% of neonatal rat and 68% of hPSC-CMs recovered the Z-disc loss within 24 h. Significant differences to control cells, after the Z-disc loss, in terms of cell perimeter, x- and y-expansion and calcium homeostasis were not found. Only 14 days in vitro old hPSC-CMs reacted with a significant decrease in cell area, x- and y-expansion 24 h past nanosurgery. This demonstrates that CMs can compensate the loss of a single Z-disc and recover a regular sarcomeric pattern during spontaneous contraction. It also highlights the significant potential of fs laser-based nanosurgery to physically micro manipulate CMs to investigate cytoskeletal functions and organization of single elements. Nature Publishing Group UK 2019-03-06 /pmc/articles/PMC6403391/ /pubmed/30842507 http://dx.doi.org/10.1038/s41598-019-40308-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Müller, Dominik
Hagenah, Dorian
Biswanath, Santoshi
Coffee, Michelle
Kampmann, Andreas
Zweigerdt, Robert
Heisterkamp, Alexander
Kalies, Stefan M. K.
Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
title Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
title_full Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
title_fullStr Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
title_full_unstemmed Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
title_short Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes
title_sort femtosecond laser-based nanosurgery reveals the endogenous regeneration of single z-discs including physiological consequences for cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403391/
https://www.ncbi.nlm.nih.gov/pubmed/30842507
http://dx.doi.org/10.1038/s41598-019-40308-z
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