Phase Behavior Of Lipid Membranes Research Articles

Accumulation of styrene oligomers alters lipid membrane phase order and miscibility

Growth of plastic waste in the natural environment, and in particular in the oceans, has raised the accumulation of polystyrene and other polymeric species in eukyarotic cells to the level of a credible and systemic threat. Oligomers, the smallest products of polymer degradation or incomplete polymerization reactions, are the first species to leach out of macroscopic or nanoscopic plastic materials. However, the fundamental mechanisms of interaction between oligomers and polymers with the different cell components are yet to be elucidated. Simulations performed on lipid bilayers showed changes in membrane mechanical properties induced by polystyrene, but experimental results performed on cell membranes or on cell membrane models are still missing. We focus here on understanding how embedded styrene oligomers affect the phase behavior of model membranes using a combination of scattering, fluorescence, and calorimetric techniques. Our results show that styrene oligomers disrupt the phase behavior of lipid membranes, modifying the thermodynamics of the transition through a spatial modulation of lipid composition.

Effects of the deep-sea osmolyte TMAO on the temperature and pressure dependent structure and phase behavior of lipid membranes

We studied the interaction of lipid membranes with the deep-sea osmolyte trimethalamine-N-oxide (TMAO), which is known to stabilize proteins most efficiently against various environmental stress factors, including high hydrostatic pressure (HHP). Small-angle X-ray-scattering was applied in combination with fluorescence and infrared spectroscopy, calorimetric and AFM measurements to yield insights into the influence of TMAO on the supramolecular structure, hydration level, lipid order as well as the phase behavior of one- and three-component model biomembranes, covering a large region of the temperature-pressure phase space. Our results show that TMAO has not only a marked effect on the conformational dynamics and stability of proteins and nucleic acids, but also on lipid bilayer systems. The gel-to-fluid phase transition is shifted to higher temperatures with increasing TMAO concentration, and the lipid order parameter increases in the fluid lipid phase. Strong H-bonding with bulk water and preferential exclusion of TMAO from the lipid headgroup region leads to a drastic loss of water in the interlamellar space of fully hydrated multivesicular lipid assemblies. HHP leads to an increase of the lipid order parameter of fluid membranes as well, resulting in an increase of the lipid length. Such effect is rather small, however, and the marked effect TMAO imposes on the interlamellar spacing of the lipid bilayers is not significantly affected by temperature and high pressure. Furthermore, the lateral organization of heterogeneous model membranes changes upon addition of the cosolvent. TMAO leads to a coalescence of lipid domains, probably due to an increase of the line tension between liquid ordered and disordered domains in such raft-like lipid bilayer structures.

Formation of modulated phases and domain rigidification in fatty acid-containing lipid membranes.

We investigated the phase behavior of lipid membranes containing fatty acids (FAs) by microscopy and differential scanning calorimetry. We used palmitic acid (saturated FA), oleic acid (cis-isomer of unsaturated FA), elaidic acid (trans-isomer of unsaturated FA), and phytanic acid (branched FA) and examined the effects of FAs on phase-separated structures in lipid bilayer membranes consisting of dioleolylphosphocholine (DOPC)/dipalmitoylphosphocholine (DPPC)/cholesterol (Chol). Palmitic acid and elaidic acid exclude Chol from the DPPC-rich phase. As a result, the liquid-ordered phase formed by DPPC and Chol transforms into a solid-ordered phase. Oleic acid and phytanic acid significantly reduce the line tension at the liquid domain boundary. This decrease in line tension leads to the formation of modulated phases, such as striped, hexagonal, and polygonal domains. We measured the line tension and the interdomain interaction in these specific domains by an image analysis. The result showed that oleic acid and phytanic acid-containing vesicles as well as palmitic acid-containing vesicles are not spherical, and this domain-induced deformation is explained theoretically.

Pressure Effects on Artificial and Cellular Membranes.

We review the combined effect of temperature and pressure on the structure, dynamics and phase behavior of lipid bilayers, differing in chain length, headgroup structure and composition as revealed by thermodynamic, spectroscopic and scattering experiments. The effect of additives, such as ions, cholesterol, and anaesthetics is discussed as well. Our data include also reports on the effect of pressure on the lateral organization of heterogeneous lipid membranes and lipid extracts from cellular membranes, as well as the influence of peptide and protein incorporation on the pressure-dependent structure and phase behavior of lipid membranes. Moreover, the effects of pressure on membrane protein function are summarized. Finally, we introduce pressure as a kinetic variable for studying the kinetics of various lipid phase transformations.

Effect of ring-substituted oxysterols on the phase behavior of dipalmitoylphosphatidylcholine membranes

Oxysterols are oxygenated derivatives of cholesterol that form a class of potent regulatory molecules with diverse biological activity. Given the implications of oxysterols in several physiological/pathophysiological pathways of human diseases, it is important to identify how their presence affects the biophysical properties of cell membranes. In this article we first describe the structure, formation, and biological functions of oxysterols, and previous work on the effect of these molecules on the structure and phase behavior of lipid membranes. We then present results of our X-ray diffraction experiments on aligned multilayers of dipalmitoylphosphatidylcholine (DPPC) membranes containing ring-substituted oxysterols. The effect of these molecules on the phase behavior of DPPC membranes is found to be very similar to that of cholesterol. All the oxysterols studied induce a modulated phase in DPPC membranes, similar to that reported in DPPC-cholesterol membranes. However, some differences are observed in the ability of these molecules to suppress the main transition of the lipid and to induce chain ordering, which might be related to differences in their orientation in the bilayer.

The Phase Behavior of Supported Lipid Bilayer Mixtures and Cell Membranes Imaged By Secondary Ion Mass Spectrometry

Supported lipid bilayers have been used as a tool to study the biophysical properties of model membranes with defined compositions. Special attention has been given to the role of cholesterol on the phase behavior of lipid membranes, in particular, to the formation of lipid rafts and complexes. Common techniques used to elucidate the phase behavior of binary and ternary lipid bilayers (i.e. fluorescence and atomic force microscopy) have been limited by their inability to provide direct information on the spatial composition of membranes. Secondary ion mass spectrometry (NanoSIMS) has proved to be a powerful tool for imaging the lateral organization of lipid bilayers with a spatial resolution in the order of tens of nanometers. In this study, a NanoSIMS is used to image lipid bilayers containing isotopically-labeled cholesterol. Additionally, human cell membranes are also imaged.

Effect of Hydrophobic Mismatch on Phase Behavior of Lipid Membranes

We investigate the competing effects of hydrophobic mismatch and chain stretching on the morphology and evolution of domains in lipid membranes via Monte Carlo techniques. We model the membrane as a binary mixture of particles that differ in their preferred lengths, with the shorter particles mimicking unsaturated nonraft lipids and the longer particles mimicking saturated raft lipids. We find that phase separation can be induced upon increasing either the ratio J / κ ˜ of the hydrophobic surface tension J to the compressibility modulus κ ˜ . J/ κ ˜ determines the decay length for thickness changes. When this decay length is larger than the system size the membrane remains mixed. Furthermore, increasing the thickness relaxation time can induce transient phase separation.