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Spatial presentation of cholesterol units on a DNA cube as a determinant of membrane protein-mimicking functions

Chidchob, P; Offenbartl-Stiegert, D; McCarthy, D; Luo, X; Li, J; Howorka, S; Sleiman, HF; (2018) Spatial presentation of cholesterol units on a DNA cube as a determinant of membrane protein-mimicking functions. Journal of the American Chemical Society , 141 (2) pp. 1100-1108. 10.1021/jacs.8b11898. Green open access

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Abstract

Cells use membrane proteins as gatekeepers to transport ions and molecules, catalyze reactions, relay signals, and interact with other cells. DNA nanostructures with lipidic anchors are promising as membrane protein mimics because of their high tuneability. However, the design features specifying DNA nanostructure's functions in lipid membranes are yet to be fully understood. Here, we show that altering patterns of cholesterol units on a cubic DNA scaffold dramatically changes its interaction mode with lipid membranes. This results in simple design rules that allow a single DNA nanostructure to reproduce multiple membrane protein functions: peripheral anchoring, nanopore behavior and conformational switching to reveal membrane-binding units. Strikingly, the DNA-cholesterol cubes constitute the first open-walled DNA nanopores, as only a quarter of their wall is made of DNA. This functional diversity can increase our fundamental understanding of membrane phenomena, and results in sensing, drug delivery and cell manipulation tools.

Type: Article
Title: Spatial presentation of cholesterol units on a DNA cube as a determinant of membrane protein-mimicking functions
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/jacs.8b11898
Publisher version: https://doi.org/10.1021/jacs.8b11898
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10066630
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