Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading
| Autor: | Giancarlo Forte, Antonio Pompeiano, Katarína Melajová, Jan Vrbsky, Petr Filipensky, Francesco Capradossi, Jorge Oliver-De La Cruz, Ana Rubina Perestrelo, Giorgia Nardone |
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| Rok vydání: | 2019 |
| Předmět: |
Transcription
Genetic Cell Biophysics Bioengineering 02 engineering and technology Biomaterials Focal adhesion 03 medical and health sciences Mechanobiology Cell Movement Cell Line Tumor Adipocytes medicine Humans Phosphorylation Psychological repression Adaptor Proteins Signal Transducing Cell Proliferation 030304 developmental biology Cell Nucleus Focal Adhesions 0303 health sciences Adipogenesis Chemistry Mesenchymal stem cell Transdifferentiation YAP-Signaling Proteins Mechanics Cellular Reprogramming 021001 nanoscience & nanotechnology Actins Extracellular Matrix medicine.anatomical_structure Adipose Tissue Mechanics of Materials Ceramics and Composites 0210 nano-technology Transcription Factors |
| Zdroj: | Biomaterials. 205:64-80 |
| ISSN: | 0142-9612 |
| Popis: | The mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells (MSCs). MSC fate decision can be unbalanced by controlling substrate mechanics, in turn altering the transmission of tension through cell cytoskeleton. MSCs have been proposed for orthopedic and reconstructive surgery applications. Thus, a tight control of their adipogenic potential is required in order to avoid their drifting towards fat tissue. Substrate mechanics has been shown to drive MSC commitment and to regulate YAP/TAZ protein shuttling and turnover. The mechanism by which YAP/TAZ co-transcriptional activity is mechanically regulated during MSC fate acquisition is still debated. Here, we design few bioengineering tools suited to disentangle the contribution of mechanical from biological stimuli to MSC adipogenesis. We demonstrate that the mechanical repression of YAP happens through its phosphorylation, is purely mediated by cell spreading downstream of substrate mechanics as dictated by dimensionality. YAP repression is sufficient to prompt MSC adipogenesis, regardless of a permissive biological environment, TEAD nuclear presence or focal adhesion stabilization. Finally, by harnessing the potential of YAP mechanical regulation, we propose a practical example of the exploitation of adipogenic transdifferentiation in tumors. |
| Databáze: | OpenAIRE |
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