Recapitulating the Lateral Organization of Membrane Receptors at the Nanoscale

Seyed R. Tabaei*, Marcos Fernandez-Villamarin, Setareh Vafaei, Lorcan Rooney, Paula M. Mendes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Many cell membrane functions emerge from the lateral presentation of membrane receptors. The link between the nanoscale organization of the receptors and ligand binding remains, however, mostly unclear. In this work, we applied surface molecular imprinting and utilized the phase behavior of lipid bilayers to create platforms that recapitulate the lateral organization of membrane receptors at the nanoscale. We used liposomes decorated with amphiphilic boronic acids that commonly serve as synthetic saccharide receptors and generated three lateral modes of receptor presentationrandom distribution, nanoclustering, and receptor crowdingand studied their interaction with saccharides. In comparison to liposomes with randomly dispersed receptors, surface-imprinted liposomes resulted in more than a 5-fold increase in avidity. Quantifying the binding affinity and cooperativity proved that the boost was mediated by the formation of the nanoclusters rather than a local increase in the receptor concentration. In contrast, receptor crowding, despite the presence of increased local receptor concentrations, prevented multivalent oligosaccharide binding due to steric effects. The findings demonstrate the significance of nanometric aspects of receptor presentation and generation of multivalent ligands including artificial lectins for the sensitive and specific detection of glycans.
Original languageEnglish
Pages (from-to)10327-10336
Number of pages10
JournalACS Nano
Volume17
Issue number11
Early online date18 May 2023
DOIs
Publication statusPublished - 13 Jun 2023

Keywords

  • nanoclusters
  • multivalent interaction
  • receptor crowding
  • membrane receptor
  • surface molecular imprinting

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