Precision Surface Microtopography Regulates Cell Fate via Changes to Actomyosin Contractility and Nuclear Architecture.
James CarthewHazem H AbdelmaksoudMargeaux Hodgson-GarmsStella AslanoglouSara GhavamianRoey ElnathanJoachim P SpatzJuergen BruggerHelmut ThissenNicolas H VoelckerVictor J CadarsoJessica E FrithPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
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.
Keyphrases
- cell fate
- mesenchymal stem cells
- body mass index
- gene expression
- dna damage
- transcription factor
- poor prognosis
- induced apoptosis
- stem cells
- genome wide
- umbilical cord
- binding protein
- metabolic syndrome
- type diabetes
- single cell
- risk assessment
- bone marrow
- dna methylation
- insulin resistance
- signaling pathway
- sensitive detection
- physical activity
- adipose tissue
- oxidative stress
- long non coding rna
- cell death
- amino acid
- human health