RT Journal Article SR Electronic T1 Cell-Int: a cell–cell interaction assay to identify native membrane protein interactions JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202402844 DO 10.26508/lsa.202402844 VO 7 IS 11 A1 Aymoz-Bressot, Thibaud A1 Canis, Marie A1 Meurisse, Florian A1 Wijkhuisen, Anne A1 Favier, Benoit A1 Mousseau, Guillaume A1 Dupressoir, Anne A1 Heidmann, Thierry A1 Bacquin, Agathe YR 2024 UL http://www.life-science-alliance.org/content/7/11/e202402844.abstract AB Intercellular protein–protein interactions (PPIs) have pivotal roles in biological functions and diseases. Membrane proteins are therefore a major class of drug targets. However, studying such intercellular PPIs is challenging because of the properties of membrane proteins. Current methods commonly use purified or modified proteins that are not physiologically relevant and hence might mischaracterize interactions occurring in vivo. Here, we describe Cell-Int: a cell interaction assay for studying plasma membrane PPIs. The interaction signal is measured through conjugate formation between two populations of cells each expressing either a ligand or a receptor. In these settings, membrane proteins are in their native environment thus being physiologically relevant. Cell-Int has been applied to the study of diverse protein partners, and enables to investigate the inhibitory potential of blocking antibodies, as well as the retargeting of fusion proteins for therapeutic development. The assay was also validated for screening applications and could serve as a platform for identifying new protein interactors.All data generated or analyzed during this study are included in this article and its supplementary information files, or can be available from the corresponding author upon request.