Nanopore Design and Engineering
Where Chemistry, Biology and Nanotechnology meet up
One of the main focus in our laboratory is to design and re-engineer membrane proteins and nanopores to modify their properties.
We use a range of techniques including directed evolution, genetic engineering, bioorthogonal chemical modifications (e.g. by covalently attaching DNA molecules) and computational approaches (with Prof. S. Marrink) to introduce target functions to the nanopore.
Nanopore design and engineering
Virtually all cells make proteins that form nanoscale holes on biological membranes, thus hundreds of biological nanopores are available. However, today only a few nanopores with different size, shape and properties are available. One important line of research in our laboratory is to characterise nanopores which structure is available (Figure below). Another is the de novo design nanopores with tailored properties.
Origin of Membrane Proteins
Arguably, one of the first events of cellular life was the formation of a permeable protective barrier that allowed the communication between the cell and the environment. We are aiming to recreate the spark that ignited cellular life by designing, engineering and evolving molecular components that specifically control cellular communication.
Willems K , Ruic D, Lucas F, Barman U, Hofkens J, Maglia G and Van Dorpe P. Accurate modeling of a biological nanopore with an extended continuum framework. Nanoscale (2020) DOI: 10.1039/D0NR03114C
Huang G, Willems K, Bartelds M, Van Dorpe P, Soskine M, and Maglia G. Electro-osmotic vortices promote the capture of folded proteins by PlyAB nanopores. Nano Lett. (2020). https://doi.org/10.1021/acs.nanolett.0c00877
Mutter N, Volarić J, Szymanski W, Feringa B, Maglia, G. Reversible photo-controlled nanopore assembly. JACS. (2019) doi.org/10.1021/jacs.9b06998
Nomidis SK, Hooyberghs J, Maglia G, and Carlon E. DNA capture into the ClyA nanopore: diffusion-limited versus reaction-limited processes. J Phys Condens Matter. (2018) Aug 1. (2018) 30(30):304001. doi: 10.1088/1361-648X/aacc01 DOI: 10.1088/1361-648X/aacc01
Franceschini L, Brouns T, Willems K, Carlon E, and Maglia G. DNA Translocation through Nanopores at Physiological Ionic Strengths Requires Precise Nanoscale Engineering. ACS Nano (2016). DOI: 10.1021/acsnano.6b03159. PDF
Wloka C, Mutter NL, Soskine M, and Maglia G. Alpha-helical Fragaceatoxin C nanopore engineered for double stranded and single stranded nucleic acid analysis. Angewandte Chemie Int Ed Engl. DOI: 10.1002/anie.201606742. PDFHo CW, Van Meervelt V, Tsai KC, De Temmerman PJ, Mast J, and Maglia G. Engineering a nanopore with co-chaperonin function. Science Advances. (2015) DOI: 10.1126/sciadv.1500905.
Soskine, M, Biesemans, A, De Maeyer, M, and Maglia, G. Tuning the Size and Properties of ClyA Nanopores Assisted by Directed Evolution. J Am Chem Soc (2013). DOI: 10.1021/ja4053398 -Highlight in ChemistryViews