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

authored by

Dominik Müller, Dorian Hagenah, Santoshi Biswanath, Michelle Coffee, Andreas Kampmann, Robert Zweigerdt, Alexander Heisterkamp, Stefan M.K. Kalies

Abstract

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.

Organisation(s)

Institute of Quantum Optics

External Organisation(s)

NIFE - Lower Saxony Centre for Biomedical Engineering, Implant Research and Development
REBIRTH Research Center for Translational Regenerative Medicine
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO)
Hannover Medical School (MHH)

Type

Article

Journal

Scientific Reports

Volume

9

Pages

3625

ISSN

2045-2322

Publication date

06.03.2019

Publication status

E-pub ahead of print

Peer reviewed

Yes

ASJC Scopus subject areas

General

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1038/s41598-019-40308-z (Access: Open)
https://doi.org/10.15488/10472 (Access: Open)