Permeation pathway of two hydrophobic carbon nanoparticles across a lipid bilayer

The emerging area of carbon-based nanoparticles (NPs) and their increased usage in the biomedical field necessitate checking their biocompatibility and permeation pathway across the cell membrane. In this study, we explore the permeation pathway of two NPs - a well-studied fullerene (C-60) and a pristine carbon dot (CD) across a model Palmitoyloleoylphosphatidylcholine (POPC) lipid membrane. Both constrained and unconstrained all-atom molecular dynamics (MD) simulations are carried out to understand their permeation mechanism. C-60 permeates the bilayer via passive permeation and stays inside the hydrophobic core, while the CD does not show any sign of permeation across the membrane throughout the simulation time window. The free energy profiles for the permeation are calculated using the umbrella sampling method. The huge barrier for the permeation of the CD is confirmed from the PMF profiles, while the free energy minima for the permeation of C-60 are located in the bilayer interior. This mode of permeation of C-60 can hint at its toxic nature to cell membranes widely investigated in the past. The structural properties of the bilayer are also analyzed, and on a global scale, it shows no significant mechanical damage to the membrane. Thus, our study details the molecular level interaction of pristine carbon-based NPs with a lipid bilayer. Graphic abstract Synopsis In this work, we explored the permeation pathway of two hydrophobic carbon nanoparticles (NPs) - fullerene (C-60) and carbon dot (CD) across a lipid bilayer. We assessed the free energy profile for the permeation, partition coefficient, permeability coefficient, and effects of the nanoparticles on the membrane structure.