Biomimetic Lipid Raft: Domain Stability and Interaction with Physiologically Active Molecules.

The cell membrane, also called the plasma membrane, is the membrane on the cytoplasmic surface that separates the extracellular from the intracellular. It is thin, about 10 nm thick when viewed with an electron microscope, and is composed of two monolayers of phospholipid membranes (lipid bilayers) containing many types of proteins. It is now known that this cell membrane not only separates the extracellular from the intracellular, but is also involved in sensory stimuli such as pain, itching, sedation, and excitement.

Lateral Transport of Domains in Anionic Lipid Bilayer Membranes under DC Electric Fields: A Coarse-Grained Molecular Dynamics Study.

Dynamic lateral transport of lipids, proteins, and self-assembled structures in biomembranes plays a crucial role in diverse cellular processes. In this study, we perform coarse-grained molecular dynamics simulations on a vesicle composed of a binary mixture of neutral and anionic lipids to investigate the lateral transport of individual lipid molecules and the self-assembled lipid domains upon an applied direct current (DC) electric field. Under the potential force of the electric field, a phase-separated domain rich in anionic lipids is trapped in the opposite direction of the electric field.

Recent research advances on non-linear phenomena in various biosystems.

All biological phenomena can be classified as open, dissipative and non-linear. Moreover, the most typical phenomena are associated with non-linearity, dissipation and openness in biological systems. In this review article, four research topics on non-linear biosystems are described to show the examples from various biological systems.

Physical Concept to Explain the Regulation of Lipid Membrane Phase Separation under Isothermal Conditions.

Lateral phase separation within lipid bilayer membranes has attracted considerable attention in the fields of biophysics and cell biology. Living cells organize laterally segregated compartments, such as raft domains in an ordered phase, and regulate their dynamic structures under isothermal conditions to promote cellular functions. Model membrane systems with minimum components are powerful tools for investigating the basic phenomena of membrane phase separation.

Coarse-grained molecular dynamics simulation of cation distribution profiles on negatively charged lipid membranes during phase separation.

Revealing the ion distributions on a charged lipid membrane in aqueous solution under the influence of long-range interactions is essential for understanding the origin of the stability of the bilayer structure and the interaction between biomembranes and various electrolytes. However, the ion distributions and their dynamics associated with the phase separation process of the lipid bilayer membrane are still unclear. We perform coarse-grained molecular dynamics simulations to reveal the Na and Cl distributions on charged phospholipid bilayer membranes during phase separation.

Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery.

Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking.

Suppression of Amyloid-β Adsorption on Endoplasmic Reticulum Stress-Mimicking Membranes by α-Tocopherol and α-Tocotrienol.

Two forms of hydrophobic vitamin E (VE), α-tocopherol (Toc) and α-tocotrienol (Toc3), have been proposed to be effective against Alzheimer's disease (AD), the etiology of which is thought to involve endoplasmic reticulum (ER) stress. However, previous studies reported conflicting effects of Toc and Toc3 on the risk of AD. We prepared liposomes mimicking the phase separation of the ER membrane (solid-ordered/liquid-disordered phase separation) and studied how VE can influence the interaction between amyloid-β (Aβ) and the ER membrane.

Control of Line Tension at Phase-Separated Lipid Domain Boundaries: Monounsaturated Fatty Acids with Different Chain Lengths and Osmotic Pressure.

Line tension at phase-separated lipid domain boundaries is an important factor that governs the stability of the phase separation. We studied the control of the line tension in lipid membranes composed of dioleoylphosphocholine (DOPC), dipalmitoylphosphocholine (DPPC), and cholesterol (Chol) by the addition of the following three monounsaturated fatty acids (MUFAs) with different chain lengths: palmitoleic acid (PaA), oleic acid (OA), and eicosenoic acid (EiA). In addition, we attempted to alter the line tension by applying osmotic pressure.

Artificial Palmitoylation of Proteins Controls the Lipid Domain-Selective Anchoring on Biomembranes and the Raft-Dependent Cellular Internalization.

Protein palmitoylation, a post-translational modification, is universally observed in eukaryotic cells. The localization of palmitoylated proteins to highly dynamic, sphingolipid- and cholesterol-rich microdomains (called lipid rafts) on the plasma membrane has been shown to play an important role in signal transduction in cells. However, this complex biological system is not yet completely understood.

Influence of Charge Lipid Head Group Structures on Electric Double Layer Properties.

In this study we derived a model for a multicomponent lipid monolayer in contact with an aqueous solution by means of a generalized classical density functional theory and Monte Carlo simulations. Some of the important biological lipid systems were studied as monolayers composed of head groups with different shapes and charge distributions. Starting from the free energy of the system, which includes the electrostatic interactions, additional internal degrees of freedom are included as positional and orientational entropic contributions to the free energy functional.

Three-Phase Coexistence in Binary Charged Lipid Membranes in a Hypotonic Solution.

We investigated the phase separation of dioleoylphosphatidylserine (DOPS) and dipalmitoylphosphatidylcholine (DPPC) in giant unilamellar vesicles in a hypotonic solution using fluorescence and confocal laser scanning microscopy. Although phase separation in charged lipid membranes is generally suppressed by the electrostatic repulsion between the charged headgroups, osmotic stress can promote the formation of charged lipid domains. Interestingly, we observed a three-phase coexistence even in the DOPS/DPPC binary lipid mixtures.

Phase Transition from the Interdigitated to Bilayer Membrane of a Cationic Surfactant Induced by Addition of Hydrophobic Molecules.

Although the transition between a bilayer and an interdigitated membrane of a surfactant and lipid has been widely known for long, its mechanism remains unclear. This study reveals the transition mechanism of a cationic surfactant, dioctadecyldimethylammonium chloride (DODAC), through experiments and theoretical calculations. Experimentally, the transition from the interdigitated to bilayer structure in the gel phase of DODAC is found to be induced by adding hydrophobic molecules such as -alkane and its derivatives.

Osmotic-Tension-Induced Membrane Lateral Organization.

Alteration of lipid raft organization manifesting as phase separation is important for cellular processes, such as signaling and trafficking. Such behaviors and dynamics of lipid membranes can be affected by external stimuli including both physical and chemical stimuli. In this study, we focused on osmotic-tension-induced phase separation.

Coarse-grained molecular dynamics simulation for uptake of nanoparticles into a charged lipid vesicle dominated by electrostatic interactions.

We use a coarse-grained molecular dynamics simulation to investigate the interaction between neutral or charged nanoparticles (NPs) and a vesicle consisting of neutral and negatively charged lipids. We focus on the interaction strengths of hydrophilic and hydrophobic attraction and electrostatic interactions between a lipid molecule and an NP. A neutral NP passes through the lipid membrane when the hydrophobic interaction is sufficiently strong.

Effects of Capsaicin on Biomimetic Membranes.

Capsaicin is a natural compound that produces a warm sensation and is known for its remarkable medicinal properties. Understanding the interaction between capsaicin with lipid membranes is essential to clarify the molecular mechanisms behind its pharmacological and biological effects. In this study, we investigated the effect of capsaicin on thermoresponsiveness, fluidity, and phase separation of liposomal membranes.

Effect of temperature on raft-dependent endocytic cluster formation during activation of Jurkat T cells by concanavalin A.

Temperature plays an important role in the immune response. Acclimatization occurs when there are changes in ambient temperature over a long period. In this study, we used the human leukemic Jurkat T cell line to study the effect of temperature on the immune system using concanavalin A (ConA), a plant-derived immunostimulant, as a trigger for T-cell activation.

Localization of transmembrane multiblock amphiphilic molecules in phase-separated vesicles.

A series of triblock amphiphilic molecules bearing hydrophilic PEG chains at both ends of the long aromatic hydrophobic moieties were obtained serendipitously. The molecules involve linearly connected diarylethyne and diarylbutadiyne units, which show characteristic emissions upon excitation by UV light. These emissions showed red-shifts upon an increase in the solvent polarity, where the shifts are larger for the molecules with longer aromatic moieties.

Strikingly different effects of cholesterol and 7-ketocholesterol on lipid bilayer-mediated aggregation of amyloid beta (1-42).

Oxidized cholesterol has been widely reported to contribute to the pathogenesis of Alzheimer's disease (AD). However, the mechanism by which they affect the disease is not fully understood. Herein, we aimed to investigate the effect of 7-ketocholesterol (7keto) on membrane-mediated aggregation of amyloid beta (Aβ-42), one of the critical pathogenic events in AD.

Membrane permeation of giant unilamellar vesicles and corneal epithelial cells with lipophilic vitamin nanoemulsions.

Nanoemulsions of a lipophilic vitamin, retinol palmitate (vitamin A; VA), have a therapeutic effect on corneal damage. The nanoemulsion based on a triblock-type polymer surfactant with polyoxyethylene and polypropylene, EOPOEO (EOPO) showed superior efficacy, as compared with a nanoemulsion based on polyoxyethylene (60) hydrogenated castor oil (HCO). We studied the mechanism of VA nanoemulsions related to efficacy from the viewpoint of the interaction with plasma membrane-mimicking giant unilamellar vesicles (GUVs) and the plasma membrane permeation in corneal epithelial cells.

Chirality-Dependent Interaction of d- and l-Menthol with Biomembrane Models.

Chirality plays a vital role in biological membranes and has a significant effect depending on the type and arrangement of the isomer. Menthol has two typical chiral forms, d- and l-, which exhibit different behaviours. l-Menthol is known for its physiological effect on sensitivity (i.

Thermal Stability of Phase-Separated Domains in Multicomponent Lipid Membranes with Local Anesthetics.

The functional mechanisms of local anesthetics (LAs) have not yet been fully explained, despite their importance in modern medicine. Recently, an indirect interaction between channel proteins and LAs was proposed as follows: LAs alter the physical properties of lipid membranes, thus affecting the channel proteins. To examine this hypothesis, we investigated changes in thermal stability in lipid membranes consisting of dioleoylphosphocholine, dipalmitoylphosphocholine, and cholesterol by adding the LAs, lidocaine and tetracaine.

Glycosyl chains and 25-hydroxycholesterol contribute to the intracellular transport of amyloid beta (Aβ-42) in Jurkat T cells.

Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide.

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.

Coarse-grained molecular dynamics simulation of binary charged lipid membranes: Phase separation and morphological dynamics.

Biomembranes, which are mainly composed of neutral and charged lipids, exhibit a large variety of functional structures and dynamics. Here, we report a coarse-grained molecular dynamics (MD) simulation of the phase separation and morphological dynamics in charged lipid bilayer vesicles. The screened long-range electrostatic repulsion among charged head groups delays or inhibits the lateral phase separation in charged vesicles compared with neutral vesicles, suggesting the transition of the phase-separation mechanism from spinodal decomposition to nucleation or homogeneous dispersion.

Phase Diagrams and Ordering in Charged Membranes: Binary Mixtures of Charged and Neutral Lipids.

We propose a model describing the phase behavior of two-component membranes consisting of binary mixtures of electrically charged and neutral lipids. We take into account the structural phase transition (main-transition) of the hydrocarbon chains, and investigate the interplay between this phase transition and the lateral phase separation. The presence of charged lipids significantly affects the phase behavior of the multicomponent membrane.