Gold nanoparticles with surface-anchored chiral poly(acryloyl-L(D)-valine) induce differential response on mesenchymal stem cell osteogenesis

Chirality is one of the most distinctive biochemical signatures of life, and plays crucial roles in maintaining normal functions of living cells or organisms. Pioneering work from another group has demonstrated the dependency of cell differentiation on the chirality of nano-coated substrates, but the effect of the chiral surface of nanoparticles on stem cell fates has not been investigated. In this study, the influence of molecular chiral poly(acryloyl-L(D)-valine) (L(D)- PAV)-anchored gold nanoparticles (L(D)-PAV-AuNPs) on the differentiation of mesenchymal stem cells (MSCs) was investigated. Though osteogenic differentiation of MSCs was not affected by D-PAV-AuNPs, it was significantly promoted by L-PAV-AuNPs in terms of calcium deposition, alkaline phosphatase (ALP) activity, and expression of collagen type I and osteocalcin (OCN) at both mRNA and protein levels. L-PAV-AuNPs could activate the P38 mitogen-activated protein kinase (MAPK) pathway, and may exert mechanical stress on MSCs because of high amounts of internalization. These results provide new insights on surface chirality at the nanoscale as a direct regulator to guide the differentiation of MSCs, and the use of these nanomaterials for strategic regenerative medicine.