Restoration of Membrane Environments for Membrane Proteins for Structural and Functional Studies
Qiu-Xing Jiang in New Techniques for Studying Biomembranes, 2020
After the restoration of lipid membrane environments for membrane proteins, both functions and structures of membrane proteins can be studied. It has been reported that the function of reconstituted potassium channel TRAAK and K2P1 [21,22] was assessed with the pH-sensitive fluorescent dye 9-amino-2-methoxy-6-chloroacridine (ACMA). When K+ ions flow outward down the K+ gradient via either a K+ ionophore or a potassium channel, a negative potential inside liposomes is established. Then H+ flows down the electrochemical gradient via proton ionophores and quenches the fluorescence signal of ACMA. Here both the polarity and magnitude of the transmembrane potential were tuned by adjusting the chemical gradient across the lipid membrane. The establishment of a negative potential inside liposomes with the desired magnitude was confirmed by the function of the reconstituted hyperpolarization-activated cyclic nucleotide-gated potassium and sodium 2 (HCN2) channels, which open at a voltage around −120 mV [23], opposite to the BK channels (BK channels open at positive transmembrane potentials [24]). After the confirmation of the established transmembrane potential using the flux assay method, cryo-EM was used to study the dipole potential at the center of the lipid bilayer, the transmembrane potential inside liposomes, and the structure of the reconstituted large conductance voltage- and calcium-activated potassium (BK) channel. Using the RSC method, an intermediate state of the BK channel was discovered, which is not accessible by other methods.
Features of Lipid Metabolism in Diabetes Mellitus and Ischemic Heart Disease
E.I. Sokolov in Obesity and Diabetes Mellitus, 2020
The cholesterol/phospholipid ratio in all biological membranes is 1. The phospholipids in a membrane are present in approximately the following proportion: PC — 30%, PEA — 28%, and SM — 25%. As already indicated, the lipid bilayer of a membrane is its basic structural unit and maintains its liquid-crystalline state. Physiological studies showed that a lipid bilayer of an erythrocyte membrane simultaneously has fluidity and order of the structure. Owing to the order of its structure, an erythrocyte carries out a number of processes occurring between the membrane and its surroundings (the reception of information, an exchange of energy and substances). Changes in the surroundings affect the composition of an erythrocyte membrane, the degree of its “adhesion” to the endothelium of the vessels changes, and the aggregative ability is disturbed.
The cell and tissues
Peate Ian, Dutton Helen in Acute Nursing Care, 2020
The molecules that make up the lipid bilayer are phospholipids. Phospholipids are neutral fats that have had one of the three fatty acids replaced by phosphate (PO43−), which is anionic and is therefore compatible with water. The consequence of this is that the molecules have a hydrophilic (water-attracting phosphate) end and a hydrophobic (water-repelling fatty acid) end. On both layers, the hydrophilic end is on the outer face, with the hydrophobic, fatty acid end on the inside of the layer. This means that the outside of the membrane is compatible with the aqueous medium, both inside and outside the cell, but, because of the hydrophobic nature of the interior of the bilayer, water and electrolytes cannot cross the lipid sections of the membrane. The movement of electrolytes through the membrane is facilitated by protein channels.
Targeting endoplasmic reticulum stress—the responder to lipotoxicity and modulator of non-alcoholic fatty liver diseases
Published in Expert Opinion on Therapeutic Targets, 2022
Yu Luo, Qiangqiang Jiao, Yuping Chen
Lipid bilayer stress in hepatocytes also triggers ER stress and activates IRE1α and PERK [20,21]. It was found that obese mice increased their hepatic uptake of free fatty acids (FFAs) and syntheses of triglycerides (TGs), phospholipids, and sphingolipids, elevating the PC/PE ratio in their hepatic ER and activating IRE1α [16,20]. The animals fed with SFAs rather than unsaturated FAs developed severe ER stress and liver injury [13], while raising lipid saturation in ER membranes directly stimulated IRE1α [22]. Notably, lipid bilayer stress was revealed to harm the stability of the β subunit of Sec61 ER translocation complex (Sbh1) in ER membrane and led to chronic ER stress [23]. The recognition of specific sphingolipids (dihydrosphingosine and dihydroceramide) by the transmembrane structural domain of ATF6 could result in its activation [24]. In addition, as a basic component responsible for membrane fluidity, rigidity, and permeability, the abnormal cholesterol homeostasis also elicits ER stress via lipid bilayer stress. The free cholesterol (FC) overload in NAFLD animals and patients directly changes the FC/phospholipid ratio of ER membrane, stimulating IRE1α activation in hepatocytes [25]. In steatotic mice induced by acetylated low-density lipoprotein (LDL) diet, the FC rise due to the disrupted cholesteryl ester production inspired ER stress in hepatocytes, activated IRE1α, the PERK/ATF4/CHOP pathways and autophagy, and marked the NAFLD progression [26].
A thermodynamic study of F108 and F127 block copolymer interactions with liposomes at physiological temperature
Published in Journal of Liposome Research, 2022
Obed Andres Solis-Gonzalez, Juan Ramon Avendaño-Gómez, Aarón Rojas-Aguilar
The interaction between lipid membrane vesicles and amphiphilic molecules mainly involves hydrophobic interactions, whereby the monomer migrates from the bulk aqueous phase into the lipid bilayer; this is a process that can be studied using a partition model, which is widely applied in biology (Ladbury and Chowdhry 1996). Another example is a receptor–ligand system, in which the receptor is usually a protein, and the ligand can be one of a variety of molecules (e.g., DNA or lipids or drugs) that non-covalently interact with the receptor. These interactions are based on measuring very small exothermic or endothermic energetic changes that occurr when two different types of molecules interact and can be characterised by isothermal titration calorimetry (ITC). In our system, liposomes essentially play the role of the ligand, whereas poloxamers act as the receptor in an ITC experiment. The main advantage of this technique is that it can provide a picture of the thermodynamic parameters, such as the Gibbs energy and the partition coefficient, in a specific system independent of other techniques.
Tinospora Cordifolia and Arabinogalactan in combination modulates benzo(a)pyrene-induced genotoxicity during lung carcinogenesis
Published in Drug and Chemical Toxicology, 2022
Yongli Chang, Diancui Zhang, Junxia Cui, Anshoo Malhotra
The membrane fluidity is crucial for optimization of membrane dynamics of a cell. In other words, membrane fluidity is the freedom of the relative motion in the membrane lipid bilayer (Li et al.2021). These dynamic features allow rotational or lateral diffusion of molecules. BP treatment revealed an increase in E/M ratio in comparison to normal control group. On the other hand, observance of the increased E/M ratio of the probe [pyrene] signified decline in membrane microviscosity. This decline in membrane viscosity leads to rise in membrane fluidity. In other words, alterations in membrane dynamics favored cancer initiation (Kaur and Sanyal 2010, Oommen et al.2016, Bhardwaj et al.2019). The above observation could be owed to rise in lateral diffusion as noticed by recording of high degree of freedom of the probe in the hydrocarbon phase. On the other hand, administration of combination of Aq.Tc and AG to BP treated rats significantly decreased the E/M ratio leading to significant decline in membrane fluidity. The observed decrease in membrane fluidity in BP treated rats could be linked with the regulatory role of combination of Aq.Tc and AG. So, it is quite clear from these observations that combination of Aq.Tc and AG are capable of regulating membrane dynamics in lung cancers cell, thereby, preventing the invasion phase of carcinogenesis.
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