Structural and Mechanical Response of Two-Component Photoswitchable Lipid Bilayer Vesicles

Abstract

Optical control of phospholipids is an attractive option for the rapid, reversible, and tunable manipulation of membrane structure and dynamics. Azo-PC, a lipid with an azobenzene group within one acyl chain, undergoes a light-induced trans-to-cis isomerization and thus arises as a powerful tool for manipulating lipid order and dynamics. Here, we report on vesicle-scale micropipette measurements and atomistic simulations to probe the elastic stretching modulus, water permeability, toughness, thickness, and membrane area upon isomerization. We investigated both dynamics and steady-state properties. In pure azo-PC membranes, we found that the molecular area in trans was 16% smaller than that in cis, the membrane's stretching modulus k A was 2.5 ± 0.3 times greater, and the water permeability P W was 3.5 ± 0.5 times smaller. We also studied mixtures of azo-PC with the miscible, unsaturated lipid DOPC. Atomistic molecular dynamics simulations show how the membrane thickness, chain order, and correlations across membrane leaflets explain the experimental data. Together, these data show how one rotating bond changes the molecular-and membrane-scale properties. These results will be useful for photopharmacology and for developing new materials whose permeability, elasticity, and toughness may be switched on demand.

Photoswitchable Endocytosis of Biomolecular Condensates in Giant Vesicles

“…The purity of azo‐PC as indicated by the producer was >99%. The synthesis and characterization of the molecule were reported in [ 19 , 37 ] and the UV/Vis spectrum of azo‐PC was reported in [ 19 , 38 ] and is displayed in Figure S9d (Supporting Information), see also [ 39 ] for effect of membrane composition on the spectra. The lipid 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine labeled with Atto 647N (Atto‐647N‐DOPE) was obtained from ATTO‐TEC GmbH, Siegen, Germany.…”

Investigating the Influence of Photoswitchable Lipids on the Structure and Dynamics of Lipid Membranes: Fundamentals and Potential Applications

“…Conformational photoswitching is a typical method for inducing reversible, site-specific structural and functional alterations , in bioactive molecules such as peptides, − protein-bound ligands, − and oligonucleotides. − A significant part of this category includes photoswitchable lipids (PSLs), capable of modifying their configuration when exposed to UV radiation. − PSLs often integrate an azobenzene moiety in their acyl chains, allowing for rapid and reversible trans-to-cis photoisomerization. ,,− The small size and hydrophobic properties of azobenzene make it suitable for lipid tail modification . When PSLs are fused to the lipid bilayer, it can affect the membrane structure, permeability, fluidity, and phase behavior under UV. − The trans-conformer with a straight chain mimics a saturated lipid, while the cis-form with a curved tail resembles an unsaturated lipid, limiting the closer approach of neighboring molecules. , This trans-to-cis conversion leads to a reduced packing density, increased membrane fluidity, and increased permeability to specific substances. ,,− This phenomenon offers an opportunity to design light-responsive liposomes that allow for controlled and sustainable drug delivery.…”