“Staying Out” Rather than “Cracking In”: Asymmetric Membrane Insertion of 12:0 Lysophosphocholine

• Published in: Langmuir 2016-11, Vol.32 (44), p.11655-11663
• Main Authors: Fan, Helen Y, Das, Dew, Heerklotz, Heiko
• Format: Article
• Language: English
• Subjects: Interface Components: Nanops, Colloids, Emulsions, Surfactants, Proteins, Polymers
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/acs.langmuir.6b03292

Interactions between detergents and model membranes are well described by the three-stage model: saturation and solubilization boundaries divide bilayer-only, bilayer–micelle coexistence, and micelle-only ranges. An underlying assumption of the model is the equilibration of detergent between the two membrane leaflets. However, many detergents partition asymmetrically at room temperature due to slow flip-flop, such as sodium dodecyl sulfate (SDS) and lysolipids. In this work, we use isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) to investigate the solubilization of unilamellar POPC vesicles by 12:0 lysophosphocholine (12:0 LPC). Flip-flop of 12:0 LPC occurs beyond the time scale of our experiments, which establish a characteristic nonequilibrated state with asymmetric distribution: 12:0 LPC partitions primarily into the outer leaflet. Increasing asymmetry stress in the membrane does not lead to membrane failure, i.e., “cracking in” as seen for alkyl maltosides and other surfactants; instead, it reduces further membrane insertion which leads to the “staying out” of 12:0 LPC in solution. At above the critical micellar concentration of 12:0 LPC in the presence of the membrane, micelles persist and accommodate further LPC but take up lipid from vesicles only very slowly. Ultimately, solubilization proceeds via the micellar mechanism (Kragh-Hansen et al., 1995). With a combination of demicellization and solubilization experiments, we quantify the molar ratio partition coefficient (0.6 ± 0.1 mM–1) and enthalpy of partitioning (6.1 ± 0.3 kJ·mol–1) and estimate the maximum detergent/lipid ratio reached in the outer leaflet (