PVDF surface charge directs stem cell fate via mechanotransduction and calcium signaling

Material properties such as rigidity, topography, and wettability significantly influence stem cell differentiation and are therefore optimized in implants. In this context, surface potential has been repeatedly, albeit inadvertently, shown to enhance osteogenesis. Here, we demonstrate that this surface property modulates cellular mechanosensing by altering the cell's perception of substrate rigidity. Specifically, we show that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on surfaces with a net zero charge, coated with collagen type I, exhibit characteristics typical of cells adhering to compliant substrates. Conversely, mesenchymal stem cells on polarized surfaces activate mechanoresponsive pathways that promote osteogenesis, as evidenced by large spreading areas, enhanced contractility, and Yes-associated protein (YAP) translocation into the nucleus. Furthermore, our data suggests that negative net surface potentials lead to the local accumulation of calcium ions, which further facilitates osteogenic differentiation. Collectively, these results show that surface potential is a powerful determinant of stem cell lineage commitment, offering a novel strategy to control cell fate in next-generation regenerative biomaterials.