Dimensionality changes actin network through lamin A and C and zyxin

Abstract

The actin cytoskeleton plays a key role in differentiation of human mesenchymal stromal cells (hMSCs), but its regulation in 3D tissue engineered scaffolds remains poorly studied. hMSCs cultured on 3D electrospun scaffolds made of a stiff material do not form actin stress fibers, contrary to hMSCs on 2D films of the same material. On 3D electrospun- and 3D additive manufactured scaffolds, hMSCs also displayed fewer focal adhesions, lower lamin A and C expression and less YAP1 nuclear localization. Together, this shows that dimensionality prevents the build-up of cellular tension, even on stiff materials. Knock down of either lamin A and C or zyxin resulted in fewer stress fibers in the cell center. Zyxin knock down reduced lamin A and C expression, but not vice versa, showing that this signal chain starts from the outside of the cell. Our study demonstrates that dimensionality changes the actin cytoskeleton through lamin A and C and zyxin, an important insight for future scaffold design, as the actin network, focal adhesions and nuclear stiffness are all critical for hMSC differentiation.