Phase Transitions in Small Isotropic Bicelles

Abstract

Isotropic phospholipid bicelles are one of the most prospective membrane mimetics for the structural studies of membrane proteins in solution. Recent works provided an almost full set of data regarding the properties of isotropic bicelles; however, one major aspect of their behavior is still under consideration: the possible mixing between the lipid and detergent in the bilayer area. This problem may be resolved by studying the lipid phase transitions in bicelle particles. In the present work, we investigate two effects: phase transitions of bilayer lipids and temperature-induced growth of isotropic bicelles using the NMR spectroscopy. We propose an approach to study the phase transitions in isotropic bicelles based on the properties of P NMR spectra of bilayer-forming lipids. We show that phase transitions in small bicelles are "fractional", particles with the liquid-crystalline and gel bilayers coexist in solution at certain temperatures. We study the effects of lipid fatty chain type and demonstrate that the behavior of various lipids in bilayers is reproduced in the isotropic bicelles. We show that the temperature-induced growth of isotropic bicelles is not related directly to the phase transition but is the result of the reversible fusion of bicelle particles. In accordance with our data, rim detergents also have an impact on phase transitions: detergents that resist the temperature-induced growth provide the narrowest and most expressed transitions at higher temperatures. We demonstrate clearly that phase transitions take place even in the smallest bicelles that are applicable for structural studies of membrane proteins by solution NMR spectroscopy. This last finding, together with other data draws a thick line under the long-lasting argument about the relevance of small isotropic bicelles. We show with certainty that the small bicelles can reproduce the most fundamental property of lipid membranes: the ability to undergo phase transition.

Molecular Dynamics Simulation of Small Molecules Interacting with Biological Membranes

“…By comparing these data in the absence and presence of a membrane-active molecule, ssNMR can be used to describe the effect of SSMIs on lipids or membrane structure. NMR can also provide information to construct phase transition diagrams of model cell membranes [63], which can subsequently be used to study the effect of SMMIs on phase transition temperatures [64]. In addition, NMR can provide structural insight into the conformation of small molecules when bound at the membrane interface [65][66][67][68].…”

Behavior of Most Widely Spread Lipids in Isotropic Bicelles

“…Large bicelles, formed with q > 2–3 for the most common compositions, can spontaneously orient in strong magnetic fields, and are referred to as “anisotropic”. , In turn, mixtures with smaller particles, which are not capable of such orientation, are named “isotropic bicelles” (IsoBs). The present work is focused on the smallest IsoBs with radii of 2.5–4.5 nm, which are a widely used membrane mimetic for protein structural studies with solution NMR spectroscopy. − A recent work has revealed that even the small IsoBs, providing the most narrow peaks in solution NMR spectra, contain a patch of lipid bilayer. This gives IsoBs a huge advantage over the detergent micelles, amphipols and organic solvents.…”

“…In our previous works we described the behavior of isotropic bicelles composed of various phosphatidylcholine lipids and several rim-forming agents. ,, Here we focus on bicelles composed of the less frequently used lipids: cholesterol, phosphatidylglycerols (PG), phosphatidylethanolamines (PE), phosphatidylserines (PS), sphingomyelins (SM) in both pure state and in mixtures with phosphatidylcholines (PC). We use [(3-cholamidopropyl)­dimethylammonio]-1-propanesulfonate (CHAPS) as a rim-forming surfactant.…”

Low-q Bicelles Are Mixed Micelles

“…36 These data agree with previously reported T m values derived from FTIR spectroscopy of various q -value bicelles; 36 however, they do not support recent NMR data indicating similar lipid/detergent mixing in low- and high- q bicelles. 52 As the q value increased, the T m asymptotically approached the melting temperature of a pure DMPC bilayer. Only for q ≥ 1.0, a T m close to that of a pure DMPC bilayer is obtained (±1 °C) in agreement with FTIR measurements.…”