Vesicles negatively charged

Hydrophobic and electrostatic properties of these lipopeptides show synergistic effects upon binding with membranes.1311 Due to the long stretch of basic amino acids the electrostatic interaction of the K-Ras4B peptide with negatively charged vesicles results in an approx. 103-fold increase in binding compared with a neutral membrane. 

Melino, S., Rufini, S., Sette, M., Morero, R., Grottesi, A., Paci, M. et al. (1999) Zn2+ ions selectively induce antimicrobial salivary peptide Histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain. Biochemistry, 38, 9626-9633. 

For liposomes, it has been shown that negatively charged vesicles tend to be removed relatively rapidly from the circulation whereas neutral vesicles tend to remain in the circulation for longer periods. 

The photoionization of zinc tetraphenylporphyrin and chlorophyll a in vesicles was also followed up by the ESR spectroscopy of rapidly frozen vesicles . It was found that the radical cation yield decreases in negatively charged vesicles and increases in positively charged vesicles. The cationic vesicles obviously favour electron escape from the photoproduced cation via the vesicle interface into bulk water negatively charged surfaces hinder the escape. 

Figure 4.30 Light-induced polymerization of cationic choline acrylate counterions on negatively charged vesicle surfaces produces a polymer net around the vesicle. ...

Effect o/ 10 min of red light irradiation on the absorption of the water soluble, tricationic dicarbocyanine dye (Kmax = 669 nm) bound to negatively charged vesicle surfaces in the presence of membrane-dissolved benzyltriphe-nylborate (A) or tetraphenylborate (B). Only the benzyl derivative donates electrons to the dye and thereby destroys it. 

Figure 3.7 Lysis of neutral vesicles (cholesterol/SOPC) and negatively charged vesicles (SOPS/SOPC), at 3 min, caused by 25 pm/ml poly 2. (A) Mn 9,950 g/mol poly(22-co-3i), (B) Mn 15,300 g/mol and (C) Mn 10,500 g/mol poly 3. Percent lysis values are given on top of the bars. Mn number average molecular weight, SOPC stearoyl-oleoyl-phosphatidylcholine and SOPS stearoyl-oleoyl-phosphatidylserine. Reproduced with permission from M.F. Ilker, K. Nusslein, G.N. Tew and E.B. Coughlin,/owmu / of American Chemical Society, 2004, 126,15870.

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

P-gp substrates are in general either neutral or cationic at physiological pH (weak bases). Weak bases can cross the lipid membrane in the uncharged form and reprotonate in the negatively charged cytosolic leaflet of the membrane. With a few exceptions (e.g., the tetraphenyl phosphonium ion, which can reach the cytosolic membrane leaflet due to charge delocalization [70]), permanently charged cations do not cross the cell membrane and therefore cannot interact with P-gp in intact cells. They can, however, insert into the cytosolic leaflet in inside-out cellular vesicles and are then transported by P-gp [42, 71]. 

Multiple physiological roles for IP6 and the diphosphoinositol polyphosphates have been proposed, including effects on endocytosis and mRNA transport [3] however, definitive evidence for many of these functions is lacking. Such studies are complicated by possible nonspecific effects of this highly negatively charged molecule. Of note is the report of an IP6/IP7-dependent protein kinase activity that phosphorylates pacsin/syndapin I, a protein involved in synaptic vesicle recycling [21]. 

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