Spontaneous formation of stable unilamellar vesicles

Abstract

Stable unilamellar vesicles form spontaneously upon mixing aqueous suspensions of long-chain lecithins (fatty acid chain lengths 14 carbons or longer) with small amounts (20 mol %) of micellar synthetic short-chain lecithins (fatty acid chain lengths 6-8 carbons). These vesicles are potentially ideal for any experiment (i.e., membrane protein reconstitution, drug delivery, etc.) that requires an easily formed, nonleaky unilamellar structure.

The mechanism of vesicle formation

“…Vesicles were formed spontaneously also by mixing long chain phospholipid with short chain phospholipid, or lysolecithin, either already in the organic phase or adding short chain phospholipid to a dispersion of MLVs (Gabriel & Roberts, 1984;Hauser, 1987).…”

“…In the mixtures of short chain (Gabriel & phospholipids which vesiculate spontaneously, a somehow different mechanism was proposed (Gabriel & Roberts, 1984). According to that model, short chain phospholipid, when added to the suspension of MLVs, dissolve in the outer monolayer, induce curvature and bud off vesicles.…”

“…They prefer a model where a gradual stripping down of the multilamellar aggregates occurs in line with the comment made by Evans (1986) that vesicles form by 'budding off' of highly curved sections of larger lipid sheets. Unfortunately none of these models is published except for a qualitative picture of vesicle formation by addition ofshort-chain phospholipid (Gabriel & Roberts, 1984). Wrigglesworth et al (1987) (Finer et al, 1972).…”

“…However, such a model was proposed for the vesicle formation by adding short chain phospholipid to MLVs (Gabriel & Roberts, 1984 As a consequence a blister is formed through which water penetrates, which ionizes the inner polar heads causing the BPF to peel off. The two methods indicate that curvature may be induced either by a change in the polar head region or in the non-polar part of the bilayer.…”

Spontaneous liposome formation induced by grafted poly(ethylene oxide) layers: Theoretical prediction and experimental verification

“…A limited number of alternative procedures that do not use external energy sources, however, have been described. Particles formed from a spontaneous vesiculation process have been reported that use temperature jumps near the phospholipid phase transition (1)(2)(3), pH jumps (4-7), and admixtures of high surface tension surfactants (8)(9)(10)(11)(12)(13)(14)(15)(16)(17), which produce vesicles that are stable within a narrow regime of solution conditions. These methods are not used, however, to produce poly(n)ethylene oxide (PEO)-modified sterically stabilized liposomes with long circulation times in vivo (18) and other commercialized liposome formulations.…”