nonlamellar

Nonlamellar refers to lipid–water assemblies that do not form the conventional lamellar, bilayer structure typical of many biological membranes. In nonlamellar phases, the assemblies exhibit high curvature, complex connectivity, or three-dimensional organization that departs from flat, stacked bilayers. Common nonlamellar architectures include inverse or inverted phases and bicontinuous cubic phases, as well as other nonlamellar mixtures such as sponge-like structures.

The main nonlamellar forms are inverse hexagonal (HII) and bicontinuous cubic phases. The HII phase consists of lipid monolayers arranged around aqueous channels to create tube-like structures with curved outer surfaces. Bicontinuous cubic phases (examples include Ia3d, Pn3m, and Im3m) feature two interwoven continuous aqueous networks separated by a continuous lipid bilayer, forming highly curved, three-dimensional landscapes. A sponge-like, isotropic L3 phase, where the aqueous and lipid domains interpenetrate without long-range order, is also considered a nonlamellar state. Lamellar phases serve as the reference bilayer arrangement.

Nonlamellar formation is influenced by lipid shape and composition, often described by the packing parameter. Lipids with a conical shape, such as phosphatidylethanolamines, and conditions that promote curvature stress—such as temperature changes, pH shifts, ionic strength, or the presence of curvature-inducing proteins—favor nonlamellar assemblies. Proteins that remodel membranes can stabilize or nucleate nonlamellar intermediates during fusion and fission.

Biological relevance includes roles in membrane remodeling, fusion, and trafficking, where transient nonlamellar intermediates facilitate pore formation and fusion pathways. In research and technology, nonlamellar lipid phases are exploited in drug delivery, nanomaterials templating, and as models for studying membrane dynamics, with detection commonly using X-ray diffraction, small-angle scattering, and cryo-electron microscopy.