Atomic Force Microscopy-single-molecule Force Spectroscopy Unveils GPCR Cell Surface Architecture

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Mar 11

PMID 35273337

Authors

Etienne Dague

Veronique Pons

Alexandre Roland

Jean-Marc Azais

Silvia Arcucci

Veronique Lachaize

Samuel Velmont

Emmanuelle Trevisiol

Du NGuyen

Jean-Michel Senard

Celine Gales

Affiliations

Soon will be listed here.

Abstract

G protein-coupled receptors (GPCRs) form the largest family of cell surface receptors. Despite considerable insights into their pharmacology, the GPCR architecture at the cell surface still remains largely unexplored. Herein, we present the specific unfolding of different GPCRs at the surface of living mammalian cells by atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS). Mathematical analysis of the GPCR unfolding distances at resting state revealed the presence of different receptor populations relying on distinct oligomeric states which are receptor-specific and receptor expression-dependent. Moreover, we show that the oligomer size dictates the receptor spatial organization with nanoclusters of high-order oligomers while lower-order complexes spread over the whole cell surface. Finally, the receptor activity reshapes both the oligomeric populations and their spatial arrangement. These results add an additional level of complexity to the GPCR pharmacology until now considered to arise from a single receptor population at the cell surface.

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