Research Goal
Morphological flexibility of cell membranes provides the foundation for the spatial organisation of living cells. The signature morphologies of cellular endomembrane systems are created at the nanoscale where specialised proteolipid complexes assemble to control membrane curvature, shape and topology. We apply novel experimental approaches combining nanomanipulations, electrophysiology and time-resolved fluorescence, confocal and TIRF microscopy to characterise mechanical properties and dynamics of biomimetic and cell membranes at the nanoscale, with particular attention to topological membrane remodelling, fusion and fission, dynamics of the force- and geometry-induced unmixing of membrane components and diffusion in complex media. We reconstitute the morphological activity of the prototype proteins controlling membrane remodelling, such as dynamin and matrix protein of enveloped viruses, using nanofabricated lipid templates to resolve subtle features of the proteolipid interactions.
Publications
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Nanoscale dynamics of Dynamin 1 helices reveals squeeze-twist deformation mode critical for membrane fission
Proc Natl Acad Sci U S A. 2024 Dec 3;121(49):e2321514121. doi: 10.1073/pnas.2321514121. Epub 2024 Nov 27. PMID: 39602273. -
Molecular sensing and manipulation of protein oligomerization in membrane nanotubes with bolaamphiphilic foldamers
J Am Chem Soc. (2023). doi: 10.1021/jacs.3c05753 -
Molecular Shape Solution for Mesoscopic Remodeling of Cellular Membranes
Review, Annual review of biophysics (2022), doi: 10.1146/annurev-biophys-011422-100054 -
Nonlinear material and ionic transport through membrane nanotubes
BBA - Biomembranes 1863 (2021) 183677, (2021) doi: 10.1016/j.bbamem.2021.183677 -
Reconstitution and real-time quantification of membrane remodeling by single proteins and protein complexes
Nat Protoc. 15(8):2443-2469. (2020) doi: 10.1038/s41596-020-0337-1. (2020) -
Electrophysiological Methods for Detection of Membrane Leakage and Hemifission by Dynamin 1
Methods Mol Biol. 2159:141-162 (2020). doi: 10.1007/978-1-0716-0676-6_11. (2020) -
Dynamic constriction and fission of endoplasmic reticulum membranes by reticulon
Nat Commun. 10(1):5327 (2019). doi: 10.1038/s41467-019-13327-7. (2019) -
Combining patch-clamping and fluorescence microscopy for quantitative reconstitution of cellular membrane processes with Giant Suspended Bilayers
Sci Rep. 9(1):7255. doi: 10.1038/s41598-019-43561-4. (2019) -
The 2018 biomembrane curvature and remodeling roadmap
Journal Of Physics D-Applied Physics 51, 34, 343001. doi: 10.1088/1361-6463/aacb98 (2018)