Passive Translocation of MXene: Balancing Hydrophobicity and Orientation in Initiating Local Phase Transition

MXenes, thin, two-dimensional materials composed of transition metal carbides, nitrides, and carbonitrides, exhibit unique properties due to their layered morphology. Notably, their hydrophilic surfaces contrast with a hydrophobic core, rendering them promising for applications in drug delivery, antibacterial coatings, and tissue regeneration. Here, we explore the mechanisms of MXene transmembrane translocation, a process crucial for biomedical applications, focusing on the interaction of MXenes with lipid bilayers. We employed single-chain mean field (SCMF) theory and all-atom (AA) simulations to analyze the energy barriers and structural dynamics during MXene translocation. Our findings reveal that the orientation and effective core hydrophobicity of MXene are pivotal in inducing an MXene-proximal local order-disorder transition in the membrane core (hereafter termed a "local phase transition"), which facilitates translocation. Specifically, perpendicular insertion relative to the bilayer surface, combined with strong hydrophobic interactions, promotes the formation of transient pores, enabling the escape of lipid-wrapped MXene flakes. Conversely, parallel orientation tends to embed MXene within the bilayer. These insights not only deepen our understanding of MXene-lipid interactions but also inform the design of MXene-based systems for targeted therapeutic delivery and cellular interactions.