Using Liprotides to Deliver Cholesterol to the Plasma Membrane

Cholesterol (chol) is important in all mammalian cells as a modulator of membrane fluidity. However, its low solubility is a challenge for controlled delivery to membranes. Here we introduce a new tool to deliver chol to membranes, namely, liprotides, i.e., protein-lipid complexes composed of a fatty acid core decorated with partially denatured protein. We focus on liprotides prepared by incubating Ca²⁺-depleted α-lactalbumin with oleic acid (OA) for 1 h at 20 °C (lip20) or 80 °C (lip80). The binding and membrane delivery properties of liprotides is compared to the widely chol transporter methyl-β-cyclodextrin (mBCD). Both lip20 and lip80 increase the solubility of chol ~ 50% more than mBCD and deliver chol to membranes with comparable efficiency. Although OA is cytotoxic at high concentrations, its effects are counterbalanced by chol. Further, cytotoxicity is strongly reduced when OA is replaced by cis-palmitoleic acid or cis-vaccenic acid. This makes liprotides good tools to deliver chol to membranes and cells.