Probing the interaction mechanisms of lipid nanoparticle-encapsulated mRNA with surfaces of diverse functional groups: Implication for mRNA transport

[Display omitted] •The encapsulated mRNA chains are coiled and the surface charges of mRNA are screened by the surrounding lipid molecules.•Steric force dominates the interactions of mRNA-LNPs and functional groups and its strength varies with functional groups.•Hydrogen bonding and electrostatic interactions contribute to the adhesion between mRNA-LNPs and functional groups.•The adhesion force follows the trend –OH>–COOH>–NH2 > -PO3H2 ≈ –CH3.•The –OH group is the most likely binding site for mRNA-LNP attachment. The transport of mRNA plays an indispensable role in vaccine drug delivery and emerging therapies. The attachment of lipid nanoparticle encapsulating mRNA (mRNA-LNP) to biological and engineering surfaces is determined by their intermolecular and surface interactions. In this work, the interactions between mRNA-LNP and surfaces with various functional groups were investigated using atomic force microscopy. The results show that mRNA chains are coiled in LNPs, and the surface charges of mRNA are screened by the surrounding lipid molecules. Approach force curves demonstrate that the steric repulsion varies with functional groups. Force mapping reveals that the intermolecular interactions, i.e., hydrogen bonding and electrostatic interaction, contribute to the adhesion. The –OH group is suggested as the most probable binding site for mRNA-LNP attachment. This work provides new insights into mRNA transport mechanisms at biological and engineering surfaces, with useful implications for designing novel nanocarriers and developing functional surfaces for biological applications.