Unraveling the impact of lipid domains on the dimerization processes of single-molecule EGFRs of live cells

• After ligand binding, EGFR molecules may relocate to lipid raft domains.
• Unliganded species remain outside the cholesterol-enriched lipid domains.
• Lipid domains regulate transition rates between diffusion states of liganded EGFR.
• Lipid domains around two liganded EGFRs can merge during their correlated motion.

Epidermal growth factor receptor (EGFR/ErbB1) is a transmembrane protein that can drive cell growth and survival via the ligand-induced dimerization of receptors. Because dimerization is a common mechanism for signal transduction, it is important to improve our understanding of how the dimerization process and membrane structure regulate signal transduction. In this study, we examined the effect of lipid nanodomains on the dimerization process of EGFR molecules. We discovered that after ligand binding, EGFR molecules may move into lipid nanodomains. The lipid nanodomains surrounding two liganded EGFRs can merge during their correlated motion. The transition rates between different diffusion states of liganded EGFR molecules are regulated by the lipid domains. Our method successfully captures both the sensitivity of single-molecule processes and statistic accuracy of data analysis, providing insight into the connection between the mobile clustering process of receptors and the hierarchical structure of plasma membrane.

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