Biomembrane mimics

Tan H, Liu 1, Li 1, Jiang X, Xie X, Zhong Y, et al. Synthesis and hemocompatibility of biomembrane mimicing poly(carbonate urethane)s containing fluorinated aUcyl phosphatidylcholine side groups. Biomacromolecules 2006 7(9) 2591-9. 

In biological systems molecular assemblies connected by non-covalent interactions are as common as biopolymers. Examples arc protein and DNA helices, enzyme-substrate and multienzyme complexes, bilayer lipid membranes (BLMs), and aggregates of biopolymers forming various aqueous gels, e.g, the eye lens. About 50% of the organic substances in humans are accounted for by the membrane structures of cells, which constitute the medium for the vast majority of biochemical reactions. Evidently organic synthesis should also develop tools to mimic the Structure and propertiesof biopolymer, biomembrane, and gel structures in aqueous media. 

Lipophilicity is intuitively felt to be a key parameter in predicting and interpreting permeability and thus the number of types of lipophilicity systems under study has grown enormously over the years to increase the chances of finding good mimics of biomembrane models. However, the relationship between lipophilicity descriptors and the membrane permeation process is not clear. Membrane permeation is due to two main components the partition rate constant between the lipid leaflet and the aqueous environment and the flip-flop rate constant between the two lipid leaflets in the bilayer [13]. Since the flip-flop is supposed to be rate limiting in the permeation process, permeation is determined by the partition coefficient between the lipid and the aqueous phase (which can easily be determined by log D) and the flip-flop rate constant, which may or may not depend on lipophilicity and if it does so depend, on which lipophilicity scale should it be based ... 

In the context of this chapter, biomimetic is defined as the nse of simple synthetic media to mimic a complex biological process . Earlier Fendler (1984) defined membrane biomimetic chemistry as processes in simple media that mimic aspects of biomembranes . Thus, classical biomimetic approaches target specific... 

How can a stabilization of biomembranes be achieved synthetically An attempt to mimic a support similar to the spectrins seems unfeasible, for very little is known as yet about the interactions between peripheral and integral proteins. An increase of stability via polymer coatings, as in the case of bacteria membranes, sounds more realistic and is, in fact, used for immobilizing living cells. This coating however, prevents cell-cell contact and hence interaction of different cells5). 

Principles to stabilize lipid bilayers by polymerization have been outlined schematically in Fig. 4a-d. Mother Nature — unfamiliar with the radically initiated polymerization of unsaturated compounds — uses other methods to-stabilize biomembranes. Polypeptides and polysaccharide derivatives act as a type of net which supports the biomembrane. Typical examples are spectrin, located at the inner surface of the erythrocyte membrane, clathrin, which is the major constituent of the coat structure in coated vesicles, and murein (peptidoglycan) a macromolecule coating the bacterial membrane as a component of the cell wall. Is it possible to mimic Nature and stabilize synthetic lipid bilayers by coating the liposome with a polymeric network without any covalent linkage between the vesicle and the polymer One can imagine different ways for the coating of liposomes with a polymer. This is illustrated below in Fig. 53. 

Compared with lAM, which uses a monolayer of phospholipid, the liposomal phospholipid bilayers in ILC have the advantage of closely resembling biologic membrane bilayers and constitute a 2-D fluid in which lipid molecules and other components are free to diffuse (10). With this technique, the phospholipid composition can be changed to mimic the membrane of interest. Membrane lipids extracted from human cells also can be used the technique then is called immobilized biomembrane chromatography (IBC) (11). 

It was fortuitous that octanol was chosen as the solvent most likely to mimic the biomembrane. Extensive studies over the last 3 5 years (40,000experimental P-values in 400 different solvent systems) have failed to dislodge octanol from its secure perch (107,108). 

Inhibition of peroxidation of unsaturated lipid chains in biomembranes is of particular significance and interest, because uncontrolled oxidation disrupts the protective layer around cells provided by the membranes. Furthermore, radical chain transfer reactions can also initiate damage of associated proteins, enzymes and DNA. The volume of literature is immense and expanding in the field of antioxidants. We will select certain milestones of advances where micelles and lipid bilayers, as mimics of biomembranes, provided media for quantitative studies on the activities of phenolic antioxidants. One of us, L. R. C. Barclay, was fortunate to be able to spend a sabbatical in Dr. Keith Ingold s laboratory in 1979-1980 when we carried out the first controlled initiation of peroxidation in lipid bilayers of egg lecithin and its inhibition by the natural antioxidant a-Toc . A typical example of the early results is shown in Figure 4. The oxidizability of the bilayer membrane was determined in these studies, but we were not aware that phosphatidyl cholines aggregate into reverse micelles in non-protic solvents like chlorobenzene, so this determination was not correct in solution. This was later corrected by detailed kinetic and P NMR studies, which concluded that the oxidizability of a lipid chain in a bilayer is very similar to that in homogeneous solution . ... 

Although phospholipid bilayers are better mimics of biomembranes than are micelles, there are few reliable quantitative data on flavonoid antioxidant activities in lipid bilayers. Terao and coworkers compared the antioxidant efficiency of quercetin and catechins (epicatechin and epicatechin gallate) with that of a-Toc in egg yolk PC liposomes using initiation by the water-soluble initiator, ABAP, and analysis of hydroperoxide formation and antioxidant consumption by HPLC. Based on the length of the induction periods and the profile of suppressed hydroperoxide formation, they concluded that quercetin and the catechins were more efficient antioxidants than a-Toc in these bilayers. Apparently the unique behavior of a-Toc in bUayers is responsible for these results (vide supra). In hexane and alcohols solution during suppressed peroxidation of methyl linoleate, the relative antioxidant activities reversed so that the flavonoids were 5-20 times less active... 

Fig. 11 Cryo-TEM image of PMOXA-t>-PDMS-t>-PMOXA vesicles prepared by film swelling in water scale bar 200 nm. Reprinted from [187] Kita-Tokarczyk K, Grumelard J, Haefele T, Meier W. Block copolymer vesicles-using concepts from polymer chemistry to mimic biomembranes. Polymer 46 3540, Copyright (2005), with permission from Elsevier...

Kita-Tokarczyk, K., Grumelard, J., Haefele, T., Meier, W. Block copolymer vesicles—Using concepts from polymer chemistry to mimic biomembranes. Polymer 2005, 46 (11), 3540—3563. 

In order to address the characteristics of biological models, we have to first define the basic principles of biological systems that a supramolecular model may mimic. Among the most important are selective molecular recognition of a molecular entity selective and highly accelerated modification of a substrate (typieal role of enzymes) compartmentalization and selective translocation of chemical species across boundaries (typieal role of biomembranes) harvesting and transformation of energy and self-replication. 

Facilitated diffusion passive transport, the movement of specific compounds across a biomembrane from higher to lower concentration, but at a rate greater than simple diffusion. F. d. is saturable, meaning that above a certain concentration, the rate is not dependent on the substrate concentration. Furthermore, it is stereospecific and susceptible to competitive inhibition. Together, these properties indicate that the process is mediated by a carrier or pore protein in the membrane. F.d. differs from Active transport (see) in not requiring energy. A class of substances called lonophores (see) mimic the carriers of F.d. by making membranes permeable to certain ions. Antibiotics that act in this way are called transport antibiotics. 

K. Kita-Tokarczyk et al.. Block copolymer vesicles — Using concepts from polymer chemistry to mimic biomembranes. Polymer, 46(11), 3540-3563 (2005). 

---