The mechanical properties of the microenvironment and direct contact-mediated cell-cell interactions are two variables known to be important in the determination of stem cell differentiation fate, but little is known about the interplay of these cues. Here, we use a micropatterning approach on polyacrylamide gels of tunable stiffnesses to study how homotypic cell-cell contacts and mechanical stiffness affect different stages of osteogenesis of mesenchymal stem cells (MSCs). Nuclear localization of transcription factors associated with osteogenesis depended on substrate stiffness and was independent of the degree of cell-cell contact. However, expression of alkaline phosphatase, an early protein marker for osteogenesis, increased only in cells with both direct contact with neighboring cells and adhesion to stiffer substrates. Finally, mature osteogenesis, as assessed by calcium deposition, was low in micropatterned cells, even on stiff substrates and in multicellular clusters. These results indicate that substrate stiffness and the presence of neighboring cells regulate osteogenesis in MSCs.
Last updated on 09/29/2017
The publications shown here are the articles indexed by PubMed, not the complete list of the lab's publications.
Congrats to David and team on their recent publication in Nature Communications! Here, they utilized antigen presenting cell-mimetic scaffolds to tune CAR T-cell product functionality by controlling the precise level of stimulation during T-cell activation to accommodate individual differences in the donor cells. Check out the publication here: Enhancing CAR-T cell functionality in a patient-specific manner