From macro to micro: How does Pluronic disrupt cell membrane?

Although most Pluronic triblocks are non-toxic to human cells, some still cause observable cell death under certain circumstances, which may evoke severe problems during administration. However, what determines the cytotoxicity of the Pluronic triblocks remains largely unexplored.
To comprehensively understand Pluronic's impact on human cells, several models were developed, spanning from macro to micro scales. Techniques such as cell viability assessment, membrane leakage, membrane fluidity, and Quartz crystal microbalance with dissipation (QCM-D) were employed to evaluate their cytotoxicity impact. Our results indicated that the cytotoxicity of some triblocks is caused by their cell membrane-lytic ability. However, in-depth information regarding structural changes in cell membranes induced by Pluronic remains unexplored. Neutron reflection (NR), a high-resolution probing technique, is crucial for this investigation. By utilizing deuterium labelling to lipids and water, NR can trace Pluronic and determine the extent of its distribution across the lipid bilayer. Furthermore, it can elucidate the subsequent effects on the bilayer's structure, providing complementary information on Pluronic-lipid interactions.