Lipid-cell interactions: A novel mechanism of transfer of liposome-entrapped substances into cells

A new approach has been developed for studying the transfer of liposome-entrapped substances into cells. The cells are incubated with liposomes containing two markers that in the free (non-entrapped) state enter the cells at different rates. Comparison of the ratio of cell-associated markers applied either in free or in liposome-entrapped form permits the evaluation of different pathways of cellular uptake of the intraliposomal substances. When epithelial cell sheets were incubated with egg phosphatidylcholine liposomes containing two different sugars they became cell-associated at a ratio different from their initial ratio inside the liposomes. Since the cell-associated ratio was shifted towards the value observed when the cells were incubated with a mixture of the two sugars in the free state, it is suggested that the liposomes become permeable during incubation and that the liberated substances enter the cells in the free form. On the other hand, cell-liposome interaction was demonstrated by NMR measurement and gel-filtration experiments to result in transformation of small unilamellar liposomes into larger multilayered aggregates. This transformation depends on the contact of the liposomes with the cell sheet. It is supposed that interliposomal aggregation is the underlying mechanism of cell-induced leakage of liposomes.