Multicompartment lipid cubic nanoparticles with high protein upload: millisecond dynamics of formation

Membrane shapes, produced by dynamically assembled lipid/protein architectures, are crucial for both physiological functions and the design of therapeutic nanotechnologies. Here we investigate the dynamics of lipid membrane-neurotrophic BDNF protein complexes formation and ordering in nanoparticles, with the purpose of innovation in nanostructure-based neuroprotection and biomimetic nanoarchitectonics. The kinetic pathway of membrane states associated with rapidly occurring nonequilibrium self-assembled lipid/protein nanoarchitectures was determined by millisecond time-resolved small-angle X-ray scattering (SAXS) at high resolution. The neurotrophin binding and millisecond trafficking along the flexible membranes induced an unusual overlay of channel-network architectures including two coexisting cubic lattices epitaxially connected to lamellar membrane stacks. These time-resolved membrane processes, involving intercalation of discrete stiff proteins in continuous soft membranes, evidence stepwise curvature control mechanisms. The obtained three-phase liquid-crystalline nanoparticles of neurotrophic composition put forward important advancements in multicompartment soft-matter nanostructure design.