Mechanism of Solubilization of Phospholipid Liposomes, Revisited

Abstract

Solubilization of membranes by detergents, commonly described by phase diagrams, is an essential tool in membrane biochemistry and biophysics.In spite of its importance in assuring that the states of aggregation in lipid-detergent mixtures are at equilibrium, the mechanism(s) of solubilization proposed thus far are based on ambiguous analyses of indirect, not necessarily relevant evidence. Our recent analysis of the available data, particularly kinetic studies yielded better understanding of the mechanism.Specifically, at sub-solubilizing detergent concentrations, partitioning of detergent into the bilayers of small vesicles induces size growth via a disproportionation mechanism, at higher detergent concentration, in the range of co-existence of detergent-saturated vesicles and lipid-saturated mixed micelles (between the onset and completion of solubilization) electron micrographs show thread-like micelles and vesicles with pores of increasing size, in agreement with the leakage of entrapped solutes of increasing sizes. In several electro micrographs, thread-like micelles have been observed attached to perforated bilayers. These probably transient microstructures indicate that the micellization of detergent super-saturated vesicles occurs via a series of three stages: (i) bending of detergent-rich monolayers into curved thread-like cover of the perimeter of the holes, (ii) formation of thread-like micelles attached to the vesicles due to the line tension of the holes and (iii) detachment of the (most stable) mixed micelles from the vesicles. All the available data (spectroscopic, microscopic and calorimetric) are consistent with this mechanistic model.