Modeling the saturation of detergent association in mixed liposome systems

Abstract

Cells tune the lipid types present in their membranes to adjust for thermal and chemical stability, as well as to promote association and dissociation of small molecules and bound proteins. Understanding the influence of lipid type on molecule association would open doors for targeted cell therapies, in particular when molecular association is observed in the presence of competing membranes. For this reason, we modeled and experimentally observed the association of a small molecule with two membrane types present by measuring the association of the detergent Triton X-100 with two types of liposomes, egg phosphatidylcholine (ePC) liposomes and egg phosphatidic acid (ePA) liposomes, at varying ratios. We called this mixed liposomes, as each liposome population was formed from a different lipid type. Absorbance spectrometry was used to observe the stages of detergent association with mixed liposomes and to determine the detergent concentration at which the liposomes were fully saturated. A saturation model was also derived that predicts the detergent associated with each liposome type when the lipid bilayers are fully saturated with detergent. The techinical input parameters for the model are the detergent to lipid ratio and the relative absorbance intensity for each of the pure liposome species at saturation. With that, the association of detergent with any mixture of those liposome types at saturation can be determined.