Heterogeneous role of integrins in fibroblast response to small cyclic mechanical stimulus generated by a nanoporous gold actuator.

It is important to understand the effects of mechanical stimulation on cell behaviors for homeostasis. Many studies have been performed on cell responses to mechanical stimuli, but the mechanosensing mechanism is still under debate. In the present study, experiments employing molecular dynamics (MD) simulations concerning the effects of cyclic mechanical stimulus on cell proliferation were performed based on the hypothesis that mechanosensing depends on integrin types. We used a nanoporous gold (NPG) actuator to prevent transfer of a mechanical stimulus via molecules other than integrins. Surprisingly, a small cyclic strain of only 0.5% enhanced the proliferation of fibroblasts. α5ß1 and αvß3 integrins showed high sensitivity to the mechanical stimulus, whereas α1ß1 and α2ß1 integrins exhibited low mechanosensitivity. The MD simulations showed that different conformational changes of the integrin headpiece induced by binding to the ECM led to a difference in mechanosensitivity between αI and αI-less integrin types. Thus, the present study provides evidence to support the hypothesis and suggests the mechanism for the heterogeneous roles of integrins in mechanosensing.

A new mechanism for reduced cell adhesion: Adsorption dynamics of collagen on a nanoporous gold surface.

Nanostructured materials such as nanoparticles and nanoporous materials strongly affect cell behaviors such as cell viability. Because cellular uptake of nanoporous materials does not occur, mechanisms for the effects of nanoporous materials on cells are different from those of nanoparticles. The effects of nanoporous materials on cells are thought to result from large conformational changes in the extracellular matrix (ECM) induced by the nanoporous materials, although the mechanotransduction and the critical focal adhesion cluster size also have an effect on the cell response. However, we show that the adhesion of mesenchymal stem cells to a gold surface is reduced for nanoporous gold (NPG), despite the conformational changes in collagen induced by NPG being below the detection limits of the experimental analyses. The adsorption dynamics of collagen on NPG are investigated by molecular dynamics simulations to determine the origin of the reduced cell adhesion to NPG. The adsorption energy of collagen on NPG is lower than that on flat gold (FG) despite there being little difference between the global conformation of collagen segments adsorbed on NPG compared with FG. This finding is related to the surface strain of NPG and the limited movement of collagen amino acids owing to interchain hydrogen bonds. The results obtained in this study provide new insight into the interactions between nanostructured materials and the ECM.

Antibacterial activity of ultrathin platinum islands on flat gold against Escherichia coli.

Nanoporous Au exhibits high antibacterial activity (AA) without releasing reactive oxygen species or metal ions, instead its AA depends on the work function (WF) because cell walls are affected by peculiar electronic states at the surface. Based on this mechanism, a flat surface without nanostructure should show high AA if the WF of the surface is suitably tuned. To verify this, ultrathin Pt islands with high WF was fabricated on flat Au by underpotential deposition (UPD) of copper and subsequent redox replacement with Pt, and the AA of the Pt/Au substrate on Escherichia coli was evaluated. The Pt/Au substrate showed higher AA than Pt and Au surfaces, and a positive relationship between AA and WF was demonstrated. In addition, first principles calculations were performed to investigate the mechanism for the high WF of the Pt/Au substrate. The findings suggest that the high WF of the Pt/Au substrate is at least partly due to charge transfer from Au to Pt.