Lipids, polymerizable, formation

Elbert R, Laschewsky A and Ringsdorf H 1985 Hydrophilic spacer groups in polymerizable lipids— formation of biomembrane models from bulk polymerized lipids J. Am. Ohem. Soc. 107 4134-41... 

Figure 8. Formation of polymeric monolayers from polymerizable lipids (X =...

Domain formation in binary mixtures of a polymerizable lipid and non-polymerizable lipid is well established for diacetylenic lipids. The rigid diacetylenic unit facilitates the formation of enriched domains in the condensed phase of monolayers or the solid-analogous phase of bilayers. Since diacetylenes polymerize most readily in solid-like states, most studies have focused on conditions that favor domain formation. Only in the case of a mixture of a charged diacetylenic lipid and a zwitterionic PC was phase separation not observed. Ringsdorf and coworkers first reported the polymerization of a phase-separated two-dimensional assembly in 1981 [33], Monolayer films were prepared from mixtures consisting of a diacetylenicPC (6) (Fig. 5) and a nonpolymerizable distearoyl PE (DSPE). 

Since the fatty acid chains in each lipid were 18 carbons and 16 carbons, respectively, it is reasonable that they could form a mixed lipid phase. Furthermore the bis-dienoyl substitution of 15 favors the formation of crosslinked polymer networks. Ohno et al. showed that the dienoyl group associated with the sn-1 chain could be polymerized by lipid soluble initiators, e.g. AIBN, whereas the dienoyl in the sn-2 chain was unaffected by AIBN generated radicals. Conversely, radicals from a water-soluble initiator, e.g. azo-bis(2-amidinopropane) dihydrochloride (AAPD), caused the polymerization of the sn-2 chain dienoyl group, but not the sn-1 chain. These data provide clear evidence for the hypothesis of Lopez et al. that the same reactive group located in similar positions in the sn-1 and sn-2 chains of polymerizable 1,2-diacyl phospholipids are positionally inequivalent [23]. 

All four types of polymerizable lipids shown in Fig. 4 have been realized synthetically. In this context, one need not attempt to reproduce mother nature slavishly (Fendler 8)). Kunitake 9) was able to show that simple molecules like dialkyldimethyl-ammonium salts also form bilayer assemblies. Fuhrhop 10) and Kunitake U) could accomplish the formation of monolayer liposomes with molecules containing only one alkyl chain and two hydrophilic head groups. Acryloylic and methacryloylic groups (type a and d, Table 1), as well as diacetylenic, butadienic, vinylic and maleic acid groups (type b and c), have been used as polymerizable moieties. A compilation of amphiphilic, photopolymerizable molecules is given in Table 1. 

Out of a variety of polymerizable lipids tested for possible use of bilayer formation, only three systems exhibited BLM lifetimes of more than a few minutes (Table 2 26)). These BLMs were characterized by measuring their resistance and capacitance (Table 2., see26> for details). The data obtained were comparable with values obtained with egg lecithin the most frequently used material for preparing BLMs. 

Fig. 18. Scheme of formation of polymeric liposomes from polymerizable lipids 19-33)... 

Whether polymerized model membrane systems are too rigid for showing a phase transition strongly depends on the type of polymerizable lipid used for the preparation of the membrane. Especially in the case of diacetylenic lipids a loss of phase transi tion can be expected due to the formation of the rigid fully conjugated polymer backbone 20) (Scheme 1). This assumption is confirmed by DSC measurements with the diacetylenic sulfolipid (22). Figure 25 illustrates the phase transition behavior of (22) as a function of the polymerization time. The pure monomeric liposomes show a transition temperature of 53 °C, where they turn from the gel state into the liquid-crystalline state 24). During polymerization a decrease in phase transition enthalpy indicates a restricted mobility of the polymerized hydrocarbon core. Moreover, the phase transition eventually disappears after complete polymerization of the monomer 24). 

In contrast, unchanged polymerization rates for all molar ratios of a polymerizable lipid indicate the formation of monomer islands and thus complete immiscibility. 

Fabricating a supported lipid bilayer in which both monolayers are composed of polymerizable lipids results in formation of a polymeric network in each monolayer. Furthermore, if the reactive groups are located at the termini of the acyl chains, the monolayers can be covalently linked, which is inherently more stable than a HBM in which lipid polymerization occurs in only one monolayer. 

Efforts to stabilize BLMs by the use of polymerizable lipids have been successful, but the electrochemical properties of these membranes were greatly compromised and ion channel phenomena could not be observed [21]. Microfiltration and polycarbonate filters, polyimide mesh, and hydrated gels have been used successfully as stabilizing supports for the formation of black lipid films [22-25] and these systems were observed to retain their electrical and permeability characteristics [24]. Poly(octadec-l-ene-maleic anhydride) (PA-18) was found to be an excellent intermediate layer for interfacing phospholipids onto solid substrates, and is sufficiently hydrophilic to retain water for unimpeded ion transfer at the electrode-PA-18 interface [26]. Hydrostatic stabilization of solventless BLMs has been achieved by the transfer of two lipid monolayers onto the aperture of a closed cell compartment however, the use of a system for automatic digital control of the transmembrane pressure difference was necessary [27]. 

PolyiT1Grizabl6 CountGrions. Ion exchange of the coimterions of ionic lipids vs polymerizable coimterions such as choline methacrylate presents an additional route for vesicle stabilization much like the formation of the actin network of natural membranes. Photopolymerization yields vesicles with siuTace-associated polyelectrolytes. These vesicles were reported to have a similarly reduced permeability as polymerized mono-methacryloyl lipid vesicles (184). 

In contrast to this, methacrylic and diene derivatives of lipids are not only polymerizable in the solid-like, but also in the liquid-analogue phase (17,18). In addition, the pol3mierized methacrylate and diene systems exhibit a higher mobility due to non-conjugated and saturated polymer chains and are therefore more suitable for the formation of flexible membranes. 

Singh, A. Price, R. Schoen, P. E. Yager, P. Schnur, J. M. Tubule formation by hetero biofunctional polymerizable lipids synthesis and characterization. Pohmcr Preprint. 1986 27, 393-394. 

Scheme 11.8 Formation of polymer liposomes from polymerizable lipid...

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