New Mechanics in Cell-Nanomaterial Interactions: Boron Nitride Nanosheets Inducing Water Channels Across Lipid Bilayers

Understanding the interaction between two-dimensional (2D) materials and cell membranes is pivotal for nanomedicine and safe nanotechnology applications. In this study, we investigate how hexagonal boron nitride (hBN) interacts with the cell membrane by combining molecular dynamics (MD) simulations and in vitro experiments. Our MD simulations reveal that sharp hBN wedges can penetrate lipid bilayers, forming cross-membrane water channels along their exposed polar edges, a behavior not exhibited by round hBN sheets. We hypothesize that such water channels can facilitate cross-membrane transport, potentially leading to lysosomal membrane permeabilization. To test this hypothesis, we prepared two types of hBN nanosheets, the former with a cornered morphology and the latter with a round morphology, and exposed human lung epithelial cells to both hBN nanosheets. The cornered hBN with exposed polar edges resulted in a dose dependent cytotoxic effect, whereas round hBN did not cause significant toxicity, thus confirming our hypothesis. These results highlight the significance of 2D materials in facilitating nanoscale water and molecular transport across lipid membranes and have substantial implications for the design of hBN-based drug delivery systems and safe design of future advanced hBN containing composites and devices.