Transcription and translation efficiency is reduced in cholesterol-containing liposomes

Cholesterol is a crucial lipid that lowers the phase transition temperature of phospholipid membranes and enhances their stability. Artificial cells with diverse functionalities have been developed by encapsulating transcription-translation reactions within liposomes, with the expectation that cholesterol would similarly contribute to the stabilization of membrane compartments in these artificial cells. In this study, we examined whether cholesterol influences the efficiency of reactions within liposomes. Our results demonstrated that the efficiency of transcription-translation reactions decreases in liposomes containing 40 mol% cholesterol, a level comparable to that of the outer leaflet of the human cell membrane. Furthermore, this decrease in reaction efficiency was found to be independent of liposome size or the efficiency of molecule encapsulation. This study highlights the critical role of cholesterol content in the design of artificial cells and drug delivery systems via liposome fusion, emphasizing the need for careful optimization.