Beyond the standard model of solubilization: Non-ionic surfactants induce collapse of lipid vesicles into rippled bilamellar nanodiscs

Hypothesis: Although solubilization of lipid membranes has been studied extensively, questions remain regarding the structural pathways and metastable structures involved. This study investigated whether the non-ionic detergent Triton X-100 follows the classical solubilization pathway or if intermediate nanostructures are formed.Experiments: Small angle X-ray and neutron scattering (SAXS/SANS) was used in combination with trans-mission electron cryo-microscopy and cryo-tomography to deduce the structure of mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) vesicles and Triton X-100. Time-resolved SAXS and dynamic light scattering were used to investigate the kinetics of the process.Findings: Upon addition of moderate detergent amounts at low temperatures, the lipid vesicles implode into ordered rippled bilamellar disc structures. The bilayers arrange in a ripple phase to accommodate packing constraints caused by inserted TX-100 molecules. The collapse is suggested to occur through a combination of water structure destabilization by detergents flipping across the membrane and osmotic pressure causing interbilayer attraction internally. The subsequently induced ripples then stabilize the aggregates and prevent solubilization, supported by the observation that negatively charged vesicles undergo a different pathway upon TX-100 addition, forming large bicelles. The findings demonstrate the richness in assembly pathways of simple lipids and detergents and stimulate considerations for the use of certain detergents in membrane solubilization. (c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study investigates the structural pathways and metastable structures involved in the solubilization of lipid membranes using the non-ionic detergent Triton X-100. The findings reveal a unique ripple phase of ordered rippled bilamellar disc structures formed when moderate amounts of detergent are added to lipid vesicles, suggesting a combination of water structure destabilization and osmotic pressure causing interbilayer attraction. The study highlights the diversity in assembly pathways of simple lipids and detergents and their implications for membrane solubilization.