Molecular understanding of transmembrane transport of mRNA carried by graphene oxide: Effect of membrane tension

Abstract

In recent years, graphene oxide (GO) has emerged as a promising nanocarrier for targeted mRNA delivery. However, the detailed molecular mechanisms governing its transmembrane transport remain poorly understood. Here, we employ molecular simulations to systematically investigate how membrane surface tension and binding configurations influence the transmembrane behavior of GO-mRNA nanocomplexes. Our findings reveal a membrane tension-dependent entry pathway that nanocomplex entry cell from adhesion/penetration to endocytosis, suggesting a potential mechanism for tumor cell drug resistance development. Furthermore, we demonstrate distinct transmembrane dynamics process for three predominant GO-mRNA binding modes, exhibiting variations in translocation velocity, penetration depth, and resultant membrane deformation. These computational insights provide crucial theoretical guidance for engineering optimized mRNA delivery carrier, potentially advancing the biomedical application of GO-based nanoplatforms in gene therapy and precision oncology.