Nanoscale plastics being ubiquitous in the environment can cross biological barriers primarily through interactions with the cell membrane, yet there remains a lack of knowledge about the mechanisms regulating the nanoplastic–cell membrane interface. Herein, we systematically describe nanoplastics of five common materials and three aging properties, and reveal that interfacial processes including nanoplastic translocation, transformation and membrane perturbation are governed by competition of polymer–polymer and polymer–lipid interactions. Molecular simulations suggest spontaneous insertion of polystyrene and polyethylene nanoplastics into membrane, where some kinds of lipids are adsorbed and form monolayered coronas increasing the nanoplastic’s effective size, reducing its hydrophobicity, and endowing nanoplastics with negative surface charge. Polyethylene terephthalate nanoplastics of lower hydrophobicity readily penetrate through membrane with less lipids adsorbed. Polypropylene and polyvinyl chloride nanoplastics dissolve in membrane to retard their translocation and aggravate membrane perturbation. Among aging properties, decreasing size facilitates nanoplastic dissolution, and fiber-shaped nanoplastics are easier to translocate from the tip first. Different molecules are rearranged and exchanged at the charged nanoplastic–cell membrane interface to alter nanoplastic translocation and membrane remodeling. Such distinctive interactions reduce membrane fluidity and rigidity, making it less stable and apt to collapse under stress. These results uncover key roles of the polymer type and aging properties in nanoplastic’s fate and toxicity to mammalian cells.

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