Interaction of liposomes with cultured cells: Effect of serum

Abstract

The binding of sonicated liposomes (small, mainly unilamellar) by cultured rat fibroblasts and mouse L1210 cells, in the presence or absence of serum, determined as μmoles phospholipid/mg cell protein, depends on the composition of the liposomes. Negatively charged solid liposomes (phospholipids below their phase transition temperature) were bound by cells several times more than fluid liposomes were under the same conditions. There was less binding, for each type of liposome studied, in the presence of serum. Time, liposome concentration and temperature effects suggest that liposomes interact with the cultured cells studied by a two-stage process: an initial rapid step, probably adsorptive, followed by a second slower step. Cell fractionation studies showed that solid and fluid liposome phospholipids were treated similarly by the cells and equilibrated mainly at densities similar to those of plasma membrane marker enzymes. Further, after incubations with inulin entrapped in liposomes, there was no accumulation of [ 3H]inulin in lysosomal fractions. Whereas the data indicated that the liposomes studied were not endocytosed intact, there was also no evidence that ‘fluid’ liposomes rapidly fused with cells with their contents found in soluble fractions. Studies on liposomal permeability indicated, as has been suggested previously, that cholesterol is a key component for reducing the leakiness of liposomes in the presence of significant concentrations of serum. For short-term studies liposomes lacking cholesterol can be used for studies on cell binding or uptake of entrapped species, in the presence of serum, but in longer term studies the effects of serum make interpretation of data difficult in that type of liposome.