Precision surface microtopography regulates cell fate via changes to actomyosin contractility and nuclear architecture

James Carthew, Hazem H. Abdelmaksoud, Margeaux Hodgson-Garms, Stella Aslanoglou, Sara Ghavamian, Roey Elnathan, Joachim P. Spatz, Jurgen Brugger, Helmut Thissen, Nicolas H. Voelcker, Victor J. Cadarso, Jessica E. Frith

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Cells are able to perceive complex mechanical cues from their microenvironment, which in turn influences their development. Although the understanding of these intricate mechanotransductive signals is evolving, the precise roles of substrate microtopography in directing cell fate is still poorly understood. Here, UV nanoimprint lithography is used to generate micropillar arrays ranging from 1 to 10 µm in height, width, and spacing to investigate the impact of microtopography on mechanotransduction. Using mesenchymal stem cells (MSCs) as a model, stark pattern-specific changes in nuclear architecture, lamin A/C accumulation, chromatin positioning, and DNA methyltransferase expression, are demonstrated. MSC osteogenesis is also enhanced specifically on micropillars with 5 µm width/spacing and 5 µm height. Intriguingly, the highest degree of osteogenesis correlates with patterns that stimulated maximal nuclear deformation which is shown to be dependent on myosin-II-generated tension. The outcomes determine new insights into nuclear mechanotransduction by demonstrating that force transmission across the nuclear envelope can be modulated by substrate topography, and that this can alter chromatin organisation and impact upon cell fate. These findings have potential to inform the development of microstructured cell culture substrates that can direct cell mechanotransduction and fate for therapeutic applications in both research and clinical sectors.

Original languageEnglish
Article number2003186
Number of pages15
JournalAdvanced Science
Volume8
Issue number6
DOIs
Publication statusPublished - 17 Mar 2021

Keywords

  • mechanotransduction
  • mesenchymal stem/stromal cells
  • microtopography
  • osteogenesis

Cite this