Nominally identical microplastic particles from eight different manufacturers show significant differences in their ζ-potential, which influences their interactions with cells. This study demonstrates that ζ-potential determines particle-cell adhesion strength and internalization. Environmental exposure alters the ζ-potential of microplastics, leading to changes in their interactions with cells. The ζ-potential of microplastic particles is a key factor in their interactions with cells and may govern adverse effects in organisms exposed to microplastics. The study used a microfluidic platform to quantify particle-cell adhesion and internalization. Results show that particles with more negative ζ-potential adhere more strongly to cells and are internalized more readily. Environmental exposure, leading to the formation of an eco-corona, alters the ζ-potential and thus the interactions of microplastics with cells. The study highlights the importance of ζ-potential in determining the toxicity of microplastics and emphasizes the need to characterize model microplastic particles thoroughly to ensure consistent results in research. The findings suggest that even nominally identical microplastic particles can differ significantly in their interactions with cells due to variations in ζ-potential, which is influenced by manufacturing processes and environmental exposure.Nominally identical microplastic particles from eight different manufacturers show significant differences in their ζ-potential, which influences their interactions with cells. This study demonstrates that ζ-potential determines particle-cell adhesion strength and internalization. Environmental exposure alters the ζ-potential of microplastics, leading to changes in their interactions with cells. The ζ-potential of microplastic particles is a key factor in their interactions with cells and may govern adverse effects in organisms exposed to microplastics. The study used a microfluidic platform to quantify particle-cell adhesion and internalization. Results show that particles with more negative ζ-potential adhere more strongly to cells and are internalized more readily. Environmental exposure, leading to the formation of an eco-corona, alters the ζ-potential and thus the interactions of microplastics with cells. The study highlights the importance of ζ-potential in determining the toxicity of microplastics and emphasizes the need to characterize model microplastic particles thoroughly to ensure consistent results in research. The findings suggest that even nominally identical microplastic particles can differ significantly in their interactions with cells due to variations in ζ-potential, which is influenced by manufacturing processes and environmental exposure.