Catalysis-mediated dynamic ligand presentation regulates mechanosensing-metabolism coupling of stem cells

초록

The dynamic presentation of ligands on biomaterial surfaces can greatly affect cellular behaviors. However, there have been no prior studies that utilize catalysis-mediated dynamic bonds for dynamic ligand presentation and explore its impact on cellular events. In this work we employ aniline as a catalyst to enhance the dynamics of the hydrazone bond in the tether structure of ligands attached to biomaterial substrate to study the impact of such controlled dynamic ligand presentation on the mechanosensing-metabolism coupling of adherent stem cells. Gold nanoparticles, decorated with polyethylene glycol (PEG)-hydrazide, are linked to benzaldehyde-modified glass substrates through hydrazone bonds. The catalytic aniline, combined with the cell adhesive arginylglycyl-aspartic acid (RGD) peptide, is conjugated on the nanoparticle surface to facilitate the disassociation and reassociation of hydrazone bonds in the RGD tether structure. This catalysis-mediated dynamic presentation of RGD effectively regulates the Ras-related C3 botulinum toxin substrate 1 (Rac1)-dependent mechanosensing and stimulates the actin cytoskeleton rearrangement in stem cells. The enhanced release of a glycolytic enzyme (Aldolase A) due to the cytoskeleton rearrangement leads to increased glycolysis, adenosine triphosphate (ATP) generation, oxidative phosphorylation, thereby contributing to the osteogenic differentiation of human mesenchymal stem cells (hMSCs). These findings highlight the importance of chemically manipulating the dynamic ligand presentation in regulating mechanosensing-metabolism coupling and the differentiation of stem cells.

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