UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Investigation of human iPSC-derived cardiac myocyte functional maturation by single cell traction force microscopy

Wheelwright, M; Win, Z; Mikkila, JL; Amen, KY; Alford, PW; Metzger, JM; (2018) Investigation of human iPSC-derived cardiac myocyte functional maturation by single cell traction force microscopy. PLoS One , 13 (4) , Article e0194909. 10.1371/journal.pone.0194909. Green open access

[img]
Preview
Text
Win_Investigation of human iPSC-derived cardiac myocyte functional maturation by single cell traction force microscopy_VoR.pdf - Published version

Download (3MB) | Preview

Abstract

Recent advances have made it possible to readily derive cardiac myocytes from human induced pluripotent stem cells (hiPSC-CMs). HiPSC-CMs represent a valuable new experimental model for studying human cardiac muscle physiology and disease. Many laboratories have devoted substantial effort to examining the functional properties of isolated hiPSC-CMs, but to date, force production has not been adequately characterized. Here, we utilized traction force microscopy (TFM) with micro-patterning cell printing to investigate the maximum force production of isolated single hiPSC-CMs under varied culture and assay conditions. We examined the role of length of differentiation in culture and the effects of varied extracellular calcium concentration in the culture media on the maturation of hiPSC-CMs. Results show that hiPSC-CMs developing in culture for two weeks produced significantly less force than cells cultured from one to three months, with hiPSC-CMs cultured for three months resembling the cell morphology and function of neonatal rat ventricular myocytes in terms of size, dimensions, and force production. Furthermore, hiPSC-CMs cultured long term in conditions of physiologic calcium concentrations were larger and produced more force than hiPSC-CMs cultured in standard media with sub-physiological calcium. We also examined relationships between cell morphology, substrate stiffness and force production. Results showed a significant relationship between cell area and force. Implementing directed modifications of substrate stiffness, by varying stiffness from embryonic-like to adult myocardium-like, hiPSC-CMs produced maximal forces on substrates with a lower modulus and significantly less force when assayed on increasingly stiff adult myocardium-like substrates. Calculated strain energy measurements paralleled these findings. Collectively, these findings further establish single cell TFM as a valuable approach to illuminate the quantitative physiological maturation of force in hiPSC-CMs.

Type: Article
Title: Investigation of human iPSC-derived cardiac myocyte functional maturation by single cell traction force microscopy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0194909
Publisher version: https://doi.org/10.1371/journal.pone.0194909
Language: English
Additional information: © 2018 Wheelwright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: Muscle cells, Aspect ratio, Stiffness, Calcium signaling, Cell differentiation, Heart, Culture media, Polyacrylamides
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10062840
Downloads since deposit
35Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item