Nonbilayer

Nonbilayer is a term used to describe lipid assemblies that do not form the conventional phospholipid bilayer commonly found in cellular membranes. This category includes inverted-phase structures such as the inverted hexagonal phase (HII), cubic phases, and other non-lamellar arrangements, as well as transient states that depart from flat bilayers. Nonbilayer tendencies depend on the intrinsic curvature preferences of certain lipids and their packing constraints.

A key biophysical concept is spontaneous curvature. Lipids with small headgroups or bulky tails, notably phosphatidylethanolamine (PE), tend to promote negative curvature and can favor nonbilayer phases under certain conditions (temperature, pH, ionic strength). In contrast, lipids with larger headgroups, such as phosphatidylcholine, stabilize bilayer structures. The balance between bilayer and nonbilayer tendencies influences membrane behavior, especially under stress or during remodeling.

In biological membranes, nonbilayer lipids participate in dynamic processes that require curvature and remodeling, including vesicle fusion and fission, organelle morphogenesis, and the activity of curvature-sensing proteins. By stabilizing fusion intermediates or generating local curvature, these lipids modulate membrane structure and protein function at curved interfaces.

Experimental study employs techniques such as X-ray diffraction, nuclear magnetic resonance, cryo-electron microscopy, and scattering methods to detect nonbilayer phases and measure curvature propensity. Synthetic lipid systems are frequently used to isolate lipid-driven effects from proteins.

Common nonbilayer-forming lipids include PE and certain lipids with high intrinsic negative curvature, while factors like cholesterol can suppress nonbilayer tendencies and promote bilayer stability.