Molecular Dynamics Simulation of Nanometer-Sized Carbon Nitride Polyaniline (C₃N) Binding to Small Intestinal Epithelial Cell Membranes

The interaction between nanomaterials and cell membranes is pivotal as it directly correlates to their cellular penetration and cytotoxicity. Among the diverse nanomaterials, carbon nitride polyaniline (C 3 N) has emerged as a promising candidate. However, the investigation of C 3 N’s potential impact on the cell membrane has been largely overlooked. In particular, the abundant glycosphingolipids in realistic human cell membranes are frequently disregarded. In this study, employing a molecular dynamics (MD) simulation approach, we scrutinize the interaction between nanometer-sized C 3 N nanosheet and small intestinal epithelial cell (SIEC) membrane, with a primary focus on the influence of glycosphingolipids. Our MD results elucidate two prevalent binding patterns between C 3 N and the SIEC membrane: insertion and cover patterns. In the insertion pattern, C 3 N vertically permeates the SIEC membrane, eventually becoming embedded within it. Conversely, in the cover pattern, C 3 N lies parallel to the SIEC membrane. Subsequent analysis reveals that these binding patterns are dictated by initial contact. Specifically, if the initial touch occurs at a corner of C 3 N, it will insert into the SIEC membrane, whereas if the initial contact takes place along the longer edge, C 3 N will cover the SIEC membrane. Moreover, our findings demonstrate that the presence of polysaccharide chains impedes the rapid insertion of C 3 N into the SIEC membrane. In comparison, the insertion of C 3 N into a pure POPC membrane occurs significantly faster than that into the SIEC membrane, further underscoring the significance of glycosphingolipids in decelerating the insertion of C 3 N. Free energy calculations also support this finding. Consequently, our study not only unveils the pivotal role of the initial touch in guiding the binding pattern between C 3 N and the SIEC membrane but also confirms the retarding effect of glycosphingolipids on the penetration of C 3 N into the membrane, representing a significant contribution to the understanding of the 2D nanomaterial–cell membrane interaction.