(659e) Lipid Domain Pixelation Patterns Imposed By Homogeneous Nanosurfaces Fabricated By Electron Beam Lithography

Lipid molecules self-assemble into a dual leaflet form of smectic liquid crystal with fascinating properties. With the exception of compositions near a critical point, coexisting lipid phases exist as microscopic domains owing to high line energy, and their size is non-uniform. Therefore, a significant challenge exists in forming uniformly sized lipid domains existing as single addressable elements that could be arrayed at high density and provide compatibility with current nanometer-scale device elements. Formation and arraying of these domain “pixels” in a high throughput manner could be used to create optical devices, biosensor arrays, drug delivery devices, and artificial organelles where the major advantage is that the positioning of the domain pixels could be dynamically controlled by applied forces, e.g. electric fields. This work describes a technique for forming nanometer-scale pixelated lipid domains that are self-organized into geometric patterns residing on a square lattice.   In this process, a lipid multibilayer stack is deposited onto a silicon substrate patterned with a square lattice array of poly(methyl methacrilate) (PMMA) hemispherical features formed by electron beam lithography.  Lipid domain patterns are shown to be confined to the flat grid between the hemispheres and comprised of connected and individual domain pixels.  Analysis of lattices of varying sizes shows that domain pattern formation is driven by mechanical energy minimization and packing constraints.  We demonstrate single lattice sizes and a gradient in lattice size varying from the micrometer to the 100 nm scale applicable to precise arraying, patterning, and transport of biomolecules that partition to lipid domains. We study the dynamic evolution of the pixelation patterns of the liquid-ordered (L_o) phase in coexistence with the liquid-disordered phase in the lipid multibilayers, and show that the L_o phase exists transiently on the curvature-patterned sections of the substrate. This apparent metastability of the pattern derives from the high line energy of a pixelation pattern where a Boltzmann distribution shows near zero equilibrium partitioning of the L_o phase in the patterned regions. In addition, we demonstrate that the dynamics of the pattern metastability can be harnessed by implementing some simple variations to the underlying curvature substrate. This work stands as a stepping stone toward a deeper understanding of biological membranes. The well-defined nature of the domain patterns provide proof-of-concept that curvature patterning of substrates can be used to direct bending and line energy to attain cell-like dynamics.