Liposome/membrane mechanism

In spite of the overwhelming importance of the channel mechanism for the transport of alkali and alkaline earth metal ions in biological systems, only carrier transport has been studied extensively by chemists. Studies on ion channel mimics of simple structures have long been limited to antibiotic families of gramicidin, amphotericin B, and others. Several pioneers have reported successful preparation of non-peptide artificial channels. However, their claims have been based on kinetic characteristics observed for the release of metal ions through liposomal membrane and lacked the very critical proofs of channel formation. Such a situation was... 

Before concluding this review, it is appropriate to comment on estimation methods of artificial ion channels. As described in each experimental method, both planar and liposomal membranes could be used for detecting the ion transport via the channel mechanism. For estimating the ion transport rate across the liposomal membrane, a variety of methodologies have been employed. These may be summarized as follows ... 

Perhaps the simplest solvent dispersion method is that developed by Batzri and Korn (1973). Phospholipids and other lipids to be a part of the liposomal membrane are first dissolved in ethanol. This ethanolic solution is then rapidly injected into an aqueous solution of 0.16 M KC1 using a Hamilton syringe, resulting in a maximum concentration of no more than 7.5% ethanol. Using this method, single bilayer liposomes of about 25-nm diameter can be created that are indistinguishable from those formed by mechanical sonication techniques. The main disadvantages of ethanolic injection are the limited solubility of some lipids in the solvent (about 40 mM for phosphatidyl choline) and the dilute nature of the resultant liposome suspension. However, for the preparation of small quantities of SUVs, this method may be one of the best available. 

Muranushi N, Nakajima Y, Kinugawa M, et al. Mechanism for the inducement of the intestinal absorption of poorly absorbed drugs by mixed micelles. Part 2. Effect of the incorporation of various lipids on the permeability of liposomal membranes. Int J Pharm 1980 4 281-290. 

It is clear that POPC liposomes will select out and bind the hydrophobic dipeptide(s), ignoring the hydrophilic ones. If now a hydrophobic condensing agent is present on the liposome membrane, an oligomerization of the bound hydrophobic peptide, e.g. H-Trp-Trp-OH, can take place. This mechanism of selection is illustrated in Figure 5. This is indeed what happens, as shown in the experimental data illustrated in Table 1. 

Fig. 19 Left) Schematic representation of the proposed mechanism for topological changes in dioleoyl phosphoethanolamine (DOPE) based liposomal membranes upon ultrasound irradiation. Right) (a) Giant DOPE-based unilamellar vesicle, before sonication, which shows an inhomogeneous membrane DOPE-rich domains of negative curvature are marked in red, embedded in zones rich in dioleoyl phosphocholine (DOPC) of zero mean curvature, (b) Illustration of shape changes upon ultrasound stimuli. Reproduced with permission from [99]. Copyright 2014 The Royal Society of Chemistry...

Finally, a range of steroidal polyamines were found to promote transport across cell/liposome membranes or bind to nucleic acids and promote gene transfection. Although these compounds have not in general been studied as receptors, their interactions with anionic centers are presumably central to their activities. For example, 22 and 23 were incorporated in vesicle membranes and shown to discharge pH gradients across the membranes. Their mechanisms of action are... 

Mitochondrial CYP11B2 (also known as CYPllp or steroid lip-hydroxylase) is involved in the synthesis of aldosterone. Aldosterone affects the conservation of sodium, the secretion of potassium, water retention, and blood pressure. CYPl 1B2 has been shown to catalyze the terminal regio- and stereospecific hydroxylation of deoxycorticosterone to aldosterone however, the exact mechanism of this process was not solved. Rapid-quenching experiments with the membrane-bound bovine CYP11B2 incorporated into liposome membranes have demonstrated that aldosterone is produced via corticosterone and not via 18-hydroxydeoxycorticosterone. Moreover, a kinetic analysis suggested a successive mechanism of aldosterone production from corticosterone, which did not dissociate from the binding site of the enzyme [34] (Scheme 5.5). 

Abstract Membrane fusion reactions consist of three steps close apposition of membranes, mixing of lipid molecules, and formation of new bilayers in a different direction. For elucidation of the molecular mechanisms of these three steps, we have studied membrane fusion induced by amphipathic helical peptides and the protein clathrin using liposome membrane systems. Based on the results, we propose two different mechanisms of membrane close apposition close apposition of negatively or positively charged membranes occurs through the hydrophobic interaction between proteins or peptides after their electrostatic binding to the... 

Key words Amphipathic peptide -clathrin - liposome - membrane fusion - fusion mechanism... 

Cooper, C. E. Wrigglesworth, J. M. Nicholls, P. The mechanism of potassium movement across the liposomal membrane. Biochem. Biophys. Res. Commun. 1990, 173, 1008-1012. 

The mechanism responsible for improved delivery of lipophilic drugs has not yet been clarified. Absorption of liposomes by cells is unlikely. Adsorption to cells followed by slow release of the drug from the liposome, either via diffusion through the thin aqueous tear film or via direct partitioning from the membrane of the vesicle to the membrane of the cell, was proposed as a possible pathway. 

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