Self-assembly of ultra-small-sized carbon nanoparticles in lipid membrane disrupts its integrity

Although nanomaterials are widely studied in biomedical applications, the major concern of nanotoxicity still exists. Therefore, numerous studies have been conducted on the interactions of various biomolecules with various types of nanomaterials, including carbon nanotubes, graphene, fullerene etc. However, the size effect of nanomaterials is poorly documented, especially ultra-small particles. Here, the interactions of the smallest carbon nanoparticle (NP), C₂₈, with the cell membrane were studied using molecular dynamics (MD) simulations. The results show that similar to fullerene C₆₀, the C₂₈ NPs can self-assemble into stable clusters in water. Inside the membrane, the C₂₈ NPs are more prone to aggregate to form clusters than C₆₀ NPs. The reason for C₂₈ aggregation is characterized by the potential of mean force (PMF) and can be explained by the polarized nature of C₂₈ NPs while the acyl chains of lipids are nonpolar. At the C₂₈ cluster regions, the thickness of the membrane is significantly reduced by the C₂₈ aggregation. Accordingly, the membrane loses its structural integrity, and translocation of water molecules through it was observed. Thus, these results predict a stronger cytotoxicity to cells than C₆₀ NPs. The present findings might shed light on the understanding of the cytotoxicity of NPs with different sizes and would be helpful for the potential biomedical applications of carbon NPs, especially as antibacterial agents.