NSRRC Activity Report 2022

Soft Matter 039 then expected to interact with the bilayer lipids via a lipid- exchange mechanism to further solvate the membrane bilayer. In summary, the polytherapy of PMB with cubosomes achieved better antibacterial activity against a series of gram-negative bacteria than the traditional approach with PMB-loaded cubosomes. This novel approach paves the way for the future design of nanoparticle-based combination therapies. The use of state-of-the-art NR to non- destructively probe a model bacterial membrane offers a high-spatial-resolution technique for the study of antimicrobial– bacterium interaction. (Reported by Xiangfeng Lai, Monash University, Australia) This report features the work of Jian Li, Hsin-Hui Shen and their collaborators, published in Nat. Commun. 13 , 1 (2022). ANSTO PLATYPUS – Neutron Reflectometer • NR • Soft Matter, Biological Science, Polymer Chemistry, Interface and Thin-film Chemistry Reference 1. X. Lai, M.-L. Han, Y. Ding, S. H. Chow, A. P. Le Brun, C.-M. Wu, P. J. Bergen, J.-h. Jiang, H.-Y. Hsu, B. W. Muir, Nat. Commun. 13 , 1 (2022). Fig. 2 : Neutron reflectometry experiment. (a) Schematic representation of the model outer membrane bilayer. Lipid A (outer leaflet): the 1,2-dipalmitoyl-d 62 -sn-glycero-3-phosphocholine (d-DPPC, inner leaflet) membrane bilayer is absorbed on the SiO 2 surface. During the experiments, all space inside the cell is always filled with aqueous solution, i.e. , D 2 O, CMSi (contrast matched silicon), and H 2 O buffer. (b) The NR profiles (symbols) and fits (lines) of the bilayer obtained from D 2 O (black squares and line), CMSi (red circles and line), and H 2 O (blue triangles and line). The insert shows the corresponding scattering length density (SLD) profiles of the bilayer and the diagram depicts the bilayer structure and distance relative to the SiO 2 surface. (c) Experimental (symbols) and fitted (curves) NR profiles of the bilayer (black squares and line), treated with 32 µg/mL cubosomes (red circles and line) followed by 4 µg/mL PMB (blue triangles and line) in D 2 O; the black arrow indicates the fringe changing from the black to red curve after incubation with the cubosomes. (d) The corresponding SLD profiles of (c). The insert depicts the membrane bilayer after successive treatment with the cubosomes and PMB. (e) Experimental (symbols) and fitted (curves) NR profiles of the bilayer (black squares and line) treated with 4 µg/mL PMB (red circles and line) followed by 32 µg/mL cubosomes (blue triangles and line) in D 2 O; the black arrow indicates that the fringe from the black to red curve remained the same after incubation with PMB. (f) The corresponding SLD profiles of (e). The insert depicts the bilayer after successive treatment with PMB and cubosomes. [Reproduced from Ref. 1]