Biointerface Structure Effects Govern the Macropinocytosis Process for Nanoclay to Enter Cells

Macropinocytosis serves as the primary pathway for nanomaterials to enter cells. However, the dynamic processes and physical chemistry mechanisms underlying this phenomenon remain poorly understood. Here, we reveal that the uptake of nanoclay (kaolinite) into cells is predominantly influenced by biointerface structural effects, with the formation of a dynamic hydrogen-bond network at the interface playing a pivotal role. Kaolinite samples of varying sizes were obtained through centrifugal fractionation. We systematically compared interactions between kaolinite of different sizes and the same cell type, as well as between kaolinite of identical size and different cell types. Both cellular experiments and molecular dynamics simulations confirmed that the dynamic hydrogen-bond network at the interface regulates macropinocytosis, a process jointly influenced by material size and membrane composition. This study elucidates the dominant role of hydrogen bonds at the nanoclay/cell membrane interface during macropinocytosis, providing a physical chemistry perspective for its regulation.