The Effect of Selected Flavonoids and Lipoic Acid on Natural and Model Cell Membranes: Langmuir and Microelectrophoretic Methods.

The influence of kaempferol (K), myricetin (M) and lipoic acid (LA) on the properties of natural erythrocytes, isolated from animal blood and biological membrane models (monolayers and liposomes) made of phosphatidylcholine (PC), cholesterol (CHOL), and sphingomyelin (SM), CHOL in a ratio of 10:9, was investigated. The Langmuir method, Brewster angle microscopy (BAM) and microelectrophoresis were used. The presented results showed that modification of liposomes with kaempferol, myricetin and lipoic acid caused changes in the surface charge density and the isoelectric point value. Comparing the tested systems, several conclusions were made. (1) The isoelectric point for the DPPC:Chol:M (~2.2) had lower pH values compared to lipoic acid (pH~2.5) and kaempferol (pH~2.6). (2) The isoelectric point for the SM-Chol with myricetin (~3.0) had lower pH values compared to kaempferol (pH~3.4) and lipoic acid (pH~4.7). (3) The surface charge density values for the DPPC:Chol:M system in the range of pH 2-9 showed values from 0.2 to -2.5 × 10-2 C m-2. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.7 × 10-2 C m-2 and 0.8 × 10-2 C m-2) and lower at pH~9 (-2.1 × 10-2 C m-2 and -1.8 × 10-2 C m-2), respectively. (4) The surface charge density values for the SM:Chol:M system in the range of pH 2-9 showed values from 0.5 to -2.3 × 10-2 C m-2. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.8 × 10-2 C m-2), and lower at pH~9 (-1.0 × 10-2 C m-2 and -1.8 × 10-2 C m-2), respectively. (5) The surface charge density values for the erythrocytes with myricetin in the range of pH 2-9 showed values from 1.0 to -1.8 × 10-2 C m-2. Meanwhile, for the erythrocytes:K and erythrocytes:LA systems, these values, at pH~2, were 1.3 × 10-2 C m-2 and 0.8 × 10-2 C m-2 and, at pH~9, -1.7 × 10-2 C m-2 and -1.0 × 10-2 C m-2, respectively.

Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes.

The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the membrane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phospholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10-20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from reversible work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10-7 cm2/s for the cholesterol-free and cholesterol-rich setups.

How Alcoholic Disinfectants Affect Coronavirus Model Membranes: Membrane Fluidity, Permeability, and Disintegration.

Atomistic molecular dynamics simulations have been carried out with a view to investigating the stability of the SARS-CoV-2 exterior membrane with respect to two common disinfectants, namely, aqueous solutions of ethanol and n-propanol. We used dipalmitoylphosphatidylcholine (DPPC) as a model membrane material and did simulations on both gel and liquid crystalline phases of membrane surrounded by aqueous solutions of varying alcohol concentrations (up to 17.5 mol %). While a moderate effect of alcohol on the gel phase of membrane is observed, its liquid crystalline phase is shown to be influenced dramatically by either alcohol. Our results show that aqueous solutions of only 5 and 10 mol % alcohol already have significant weakening effects on the membrane. The effects of n-propanol are always stronger than those of ethanol. The membrane changes its structure, when exposed to disinfectant solutions; uptake of alcohol causes it to swell laterally but to shrink vertically. At the same time, the orientational order of lipid tails decreases significantly. Metadynamics and grand-canonical ensemble simulations were done to calculate the free-energy profiles for permeation of alcohol and alcohol/water solubility in the DPPC. We found that the free-energy barrier to permeation of the DPPC liquid crystalline phase by all permeants is significantly lowered by alcohol uptake. At a disinfectant concentration of 10 mol %, it becomes insignificant enough to allow almost free passage of the disinfectant to the inside of the virus to cause damage there. It should be noted that the disinfectant also causes the barrier for water permeation to drop. Furthermore, the shrinking of the membrane thickness shortens the gap needed to be crossed by penetrants from outside the virus into its core. The lateral swelling also increases the average distance between head groups, which is a secondary barrier to membrane penetration, and hence further increases the penetration by disinfectants. At alcohol concentrations in the disinfectant solution above 15 mol %, we reliably observe disintegration of the DPPC membrane in its liquid crystalline phase.