The study investigates the significant differences in particle-cell interactions of nominally identical polystyrene microplastic models from eight different manufacturers. Despite their apparent similarity, these particles exhibit substantial variations in their ζ-potential, which is the electrical potential of a particle in a medium at its slipping plane. The ζ-potential of the particles is further altered after environmental exposure, leading to changes in their surface properties. The researchers developed a microfluidic microscopy platform to demonstrate that the ζ-potential determines particle-cell adhesion strength and internalization into cells. They found that particles with a more negative ζ-potential bind faster, unbind slower, and adhere stronger to cells. Additionally, the ζ-potential strongly influences the internalization probability of microplastic particles into cells, with environmentally exposed particles showing higher internalization rates due to their altered surface properties. The study highlights the importance of characterizing the ζ-potential of microplastic particles to ensure consistent and reliable results in ecotoxicological studies.The study investigates the significant differences in particle-cell interactions of nominally identical polystyrene microplastic models from eight different manufacturers. Despite their apparent similarity, these particles exhibit substantial variations in their ζ-potential, which is the electrical potential of a particle in a medium at its slipping plane. The ζ-potential of the particles is further altered after environmental exposure, leading to changes in their surface properties. The researchers developed a microfluidic microscopy platform to demonstrate that the ζ-potential determines particle-cell adhesion strength and internalization into cells. They found that particles with a more negative ζ-potential bind faster, unbind slower, and adhere stronger to cells. Additionally, the ζ-potential strongly influences the internalization probability of microplastic particles into cells, with environmentally exposed particles showing higher internalization rates due to their altered surface properties. The study highlights the importance of characterizing the ζ-potential of microplastic particles to ensure consistent and reliable results in ecotoxicological studies.