Lipid asymmetry is a ubiquitous property of the lipid bilayers in cellular membranes and its maintenance and loss play important roles in cell physiology, such as blood coagulation and apoptosis. The resulting exposure of phosphatidylserine on the outer surface of the plasma membrane has been suggested to be caused by a specific membrane enzyme, scramblase, which catalyzes phospholipid flip-flop. Despite extensive research the role of scramblase(s) in apoptosis has remained elusive. Here, we show that phospholipid flip-flop is efficiently enhanced in liposomes by oxidatively modified phosphatidylcholines. A combination of fluorescence spectroscopy and molecular dynamics simulations reveal that the mechanistic basis for this property of oxidized phosphatidylcholines is due to major changes imposed by the oxidized phospholipids on the biophysical properties of lipid bilayers, resulting in a fast cross bilayer diffusion of membrane phospholipids and loss of lipid asymmetry, requiring no scramblase protein.

The oxidation of lipids has been shown to impact virtually all cellular processes. The paradigm has been that this involvement is due to interference with the functions of membrane‐associated proteins. It is only recently that methodological advances in molecular‐level detection and identification have begun to provide insights into oxidative lipid modification and its involvement in cell signaling as well as in major diseases and inflammation. Extensive evidence suggests a correlation between lipid peroxidation and degenerative neurological diseases such as Parkinson's and Alzheimer's, as well as type 2 diabetes and cancer. Despite the obvious relevance of understanding the molecular basis of the above ailments, the exact modes of action of oxidized lipids have remained elusive. In this minireview, we summarize recent findings on the biophysical characteristics of biomembranes following oxidative derivatization of their lipids, and how these altered properties are involved in both physiological processes and major pathological conditions. Lipid‐bearing, oxidatively truncated and functionalized acyl chains are known to modify membrane bulk physical properties, such as thermal phase behavior, bilayer thickness, hydration and polarity profiles, as manifest in the altered structural dynamics of lipid bilayers, leading to augmented membrane permeability, fast lipid transbilayer diffusion (flip‐flop), loss of lipid asymmetry (scrambling) and phase segregation (the formation of ‘rafts’). These changes, together with the generated reactive lipid derivatives, can be further expected to interfere with lipid–protein interactions, influencing metabolic pathways, causing inflammation, the execution phase in apoptosis and initiating pathological processes.

Molecular assemblies containing phospholipids and conjugated polydiacetylene lipids exhibit unique biochromatic properties and have attracted increasing interest in recent years as potential bio-and chemosensors. We present a detailed study of the properties of mixed films formed at the air-water interface, which consist of phospholipid molecules and diacetylene lipids. The organization of the films has been characterized by surface pressure-area isotherms. Application of atomic force microscopy, polarized optical microscopy, and UV-vis spectroscopy provides further insight into the structures and interactions of the film components. The data indicate that the two constituents in the film are miscible at low surface pressure, while segregation of phospholipid and polymer domains occurs at higher surface pressures. The distribution and interactions between the diacetylene and phospholipid domains additionally depends on the molar fraction of phospholipid in the film. Characterization of the structural properties of the polydiacetylene domains in the films points to a formation of organized trilayer and multilayer phases at high surface pressures and high diacetylene concentrations.

The thermodynamic and morphological properties of binary films of phospholipids and diacetylene lipids deposited at the air-water interface have been studied. Brewster angle microscopy (BAM) and fluorescence microscopy have been applied to investigate the formation, organization, and structure of the film domains. BAM data acquired at different temperatures, film compositions, and surface pressures reveal the appearance of distinct patterns of the diacetylenic moieties. In particular, the exceptionally high-quality BAM images point to dendritic and fractal-like appearance of the diacetylene domains; these phenomena are discussed in a framework of diffusion-limited aggregation processes. The results of the microscopy analyses further indicate that the two molecular components already segregate at low compression pressures and that the combined effects of film composition and temperature influence the occurrence of transitions between different phases within the films. This study sheds light on the molecular and cooperative features of mixed lipid/diacetylene films and further helps to understand the unique biosensing properties of these assemblies.

Planar systems--monolayers and films--constitute a useful platform for studying membrane-active peptides. Here, we summarize varied approaches for studying peptide organization and peptide-lipid interactions at the air/water interface, and focus on three representative antimicrobial membrane--associated peptides-alamethicin, gramicidin, and valinomycin. Experimental data, specifically surface pressure/area isotherms and Brewster angle microscopy images, provided information on peptide association and the effects of the lipid monolayers on peptide surface organization. In general, film analysis emphasized the effects of lipid layers in promoting peptide association and aggregation at the air/water interface. Importantly, the data demonstrated that in many cases peptide domains are phase-separated within the phospholipid monolayers, suggesting that this behavior contributes to the biological actions of membrane-active antimicrobial peptides.