Penetration of nanoparticles across a lipid bilayer: effects of particle stiffness and surface hydrophobicity.

The cellular uptake of nanoparticles (NPs) has drawn significant attention due to their great importance and potential in drug delivery, bioimaging, and specific targeting. Here, we conduct a computational study on the translocation process of soft nanoparticles with different elasticities and surface hydrophobicities through a lipid bilayer membrane. It is shown that the translocation abilities of hydrophilic NPs can be enhanced by increasing their stiffness, while the penetrability of hydrophobic NPs is weakened by increasing the particle stiffness. The free energy analysis indicates that rigid hydrophilic NPs and soft hydrophobic NPs encounter lower energy barriers during penetration. In direct translocation, different deformation modes are observed for NPs with different surface hydrophobicities during cellular internalization. Further, deformation analysis demonstrates that hydrophilic NPs are flattened in the membrane plane, while hydrophobic NPs are elongated along the membrane norm during penetration. We conclude that the elasticity of NPs has an obvious impact on their ability to penetrate across the lipid bilayer membrane through different morphological responses of hydrophilic and hydrophobic NPs. These results shed light on the coupled effects of particle elasticity and surface hydrophobicity on the cellular uptake of elastic NPs, which may provide useful guidelines for designing effective nanocarrier systems for drug delivery.