(599b) Hybrid Material Systems for Controlling Lipid Bilayer Assembly

We have developed a set of tools and techniques for controlling the assembly of lipid bilayers to produce biomimetic membrane structures. These structures can serve as platforms for fundamental studies of membrane biophysics or as biocompatible materials for the integration of biomolecules with synthetic structures.

Using a two-phase microfluidic flow system, lipid bilayers can be constructed in an "artificial cell" format that mimics the scale and geometry of eukaryotic cell membranes as well as their leaflet-to-leaflet compositional asymmetry. These artificial cells provide a unique experimental format for probing the role that compositional asymmetry plays in physiological processes. We have deployed this technique in an investigation of the passive transport of small molecular and ionic species across lipid bilayers--a phenomenon that controls the bioavailability and tissue distribution of drugs. Early results show that asymmetric membranes support directional passive transport: the permeability of the membrane depends on how its two distinct leaflets are oriented with respect to the concentration gradient of a transported species. This result has profound implications for our understanding of the role that lipid bilayers play in generating and supporting physiological concentration gradients.

Asymmetric artificial cells are also ideal platforms for investigating the mechanics of lipid bilayers. Membrane mechanics can be probed both with direct measurements based on membrane fluctuation amplitude and by analysis of membrane deformation under osmotic stress.

We have also constructed a series of hybrid lipid materials for orienting biomolecules on nanoengineered surfaces. This includes a technique for covalently attaching lipid molecules to the surfaces of carbon nanotubes that leads to the formation of well-organized molecular lipid bilayers on nanotube surfaces. These membrane-mimetic bilayers support the integration of membrane proteins with synthetic carbon nanomaterials. We have also developed a class of polymer nanogels in which the surface of a nanoscale polymer hydrogel sphere is covalently decorated with a lipid monolayer. These nanogels support the spontaneous formation of membrane-like bilayers and are potential drug delivery vehicles.