Topological and Morphological Membrane Dynamics in Giant Lipid Vesicles Driven by Monoolein Cubosomes

Angew Chem Int Ed Engl. 2024 Sep 30:e202414970. doi: 10.1002/anie.202414970. Online ahead of print.

Abstract

Lipid nanoparticles have important applications as biomedical delivery platforms and broader engineering biology applications in artificial cell technologies. These emerging technologies often require changes in the shape and topology of biological or biomimetic membranes. Here we show that topologically-active lyotropic liquid crystal nanoparticles (LCNPs) can trigger such transformations in the membranes of giant unilamellar vesicles (GUVs). Monoolein (MO) LCNPs, cubosomes with an internal nanostructure of space group I m 3 m ${Im3m}$ incorporate into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) GUVs creating excess membrane area with stored curvature stress. Using time-resolved fluorescence confocal and lattice light sheet microscopy, we observe and characterise various life-like dynamic events in these GUVs, including growth, division, tubulation, membrane budding and fusion. Our results shed new light on the interactions of LCNPs with bilayer lipid membranes, providing insights relevant to how these nanoparticles might interact with cellular membranes during drug delivery and highlighting their potential as minimal triggers of topological transitions in artificial cells.

Keywords: Artificial cells; cubosomes; lyotropic liquid crystal nanoparticles; membrane remodelling; vesicles.