Nanoplastic-Induced Antibody Liquid-liquid Phase Separation: Insights into Potential Immunotoxic Implications

The increasing environmental prevalence of micro/nano plastics (MNPs) has raised significant concerns regarding their potential impact on human health, particularly in terms of immunotoxicity. However, the direct effects of MNPs on immune molecules, especially how they may influence protein liquid-liquid phase separation (LLPS)—a critical process implicated in various aspects of immune function—remain largely unexplored. This study addresses this gap by investigating the effects of polystyrene nanoparticles (PS NPs) with different surface modifications and sizes on LLPS in immunoglobulin Y (IgY) antibodies, critical components of the avian immune system. Our findings reveal that PS-COOH NPs uniquely induce LLPS in IgY in a size-dependent manner, while PS-NH₂ and unmodified PS NPs do not. Furthermore, NP-induced LLPS disrupts IgY’s antigen-binding capability, potentially impairing immune responses. Notably, the IgY-Fc fragment shows a greater tendency for LLPS than the full-length antibody, suggesting broader implications for immune receptor interactions. These findings underscore the significant roles of nanoparticle surface chemistry, size, and antigen interactions in modulating LLPS. This study pioneers the exploration of MNPs-induced LLPS as a potential mechanism of immunotoxicity, providing crucial insights into the health risks posed by environmental MNPs and informing strategies for mitigation.