1. Supported Lipid Bilayers

Lipid bilayers supported on planar substrates are studied and used increasingly because they afford well-defined, biofunctionalizable surfaces with potential use in many areas; among them biosensors, protein dimerization, chromatographic separation, protein immobilization, and study of membrane-membrane interactions. We are interested here in knowing the mobility of individual lipids in supported lipid bilayers – a problem that is physically fundamental and highly related to potential biological sensor functions of supported bilayers.

Spatially-resolved measurements using dual-color fluorescence correlation spectroscopy (FCS) with two-photon excitation show that slaved diffusion happened between membrane associated proteins and the underlying lipids. When the bilayer surface is incompletely covered by proteins, the translational diffusion of lipids splits into two populations. A slow mode, whose magnitude is the same as that of the protein, coexists with a fast mode characteristic of naked lipid diffusion. Control experiments using molecular weight variable polyelectrolyte as adsorbate find the slow mode is inversely dependent on the degree of polymerization of the adsorbate.

Single molecule imaging (SMI) provides vivid continuous images of the lovely diffusion processes of every single lipid and protein molecules. Modified single molecule tracking programs gives out their translational diffusion magnitudes accurately, which are well consistent with the FCS results.

2. Phospholipid Liposomes

“Liposomes” (the term refers to artificially-constructed capsules of phospholipid bilayers) would be more useful, if only they could be stabilized against fusion with one another. First, they are tremendously biofunctionalizable; antibodies, protein receptors and other biosensor molecules can attach to them. Second, they comprise compartments that can be used to encapsulate and store various cargoes, such as enzymes, proteins, DNA and various drug molecules. Their small and controllable size, diameter from tens to thousands of nm, signifies that individual liposomes comprise nanocontainers with volumes from zeptoliters to femtoliters . When biomolecules or other chemical reactants are loaded into this biocompatible container, cellular processes and chemical reactions including protein expression, mRNA transcription and enzyme-catalyzed reactions can be performed inside.

There is a severe limitation, however. When liposomes encounter one another in suspension, they are prone to adhere and fuse to form a larger one. Consequently, the liposome size distribution becomes polydisperse. When liposomes encounter planar solid substrates, they fuse to form a planar supported bilayer if the solid is hydrophilic, or a planar monolayer if the surface is hydrophobic.

How to avoid vesicle fusion? A simple strategy of mixing phospholipid liposomes with charged nanoparticles and using sonication to mix them at low volume fraction is employed to produce particle-stabilized liposomes that repel one another and do not fuse. Subsequently, the volume fraction can be raised as high as 50%, reversibly, still without fusion.

Liangfang Zhang

Graduate student in Chemical Engineering Department

Current research focusing on liposome-nanoparticle complexes, dynamics of single lipids and proteins in lipid bilayers, and phases and phase transitions of biomembranes.

M.S. & B.S. from
Tsinghua University, China. Previously focused on polymer physics and polymer nanocomposite materials.