Ceramides, which are formed when sphingomyelin is hydrolyzed by sphingomyelinase, enhance several signaling processes in the plasma membrane. These ceramides induce clustering of signaling-related biomolecules, but the mechanism by which they do so remains unknown. The spatiotemporal localization of ganglioside GM1, a signaling glycolipid receptor, during sphingomyelinase-mediated hydrolysis is described in this article. We examine GM1 clustering using real-time visualization of the dynamic remodeling of the heterogeneous lipid membrane caused by sphingomyelinase action and discover that it is more complex than previously believed. To be more precise, lipid membranes generate two distinct types of condensed GM1: 1) rapidly formed but short-lived GM1 clusters that form in ceramide-rich domains nucleated from the liquid-disordered phase; and 2) late-onset but long-lived, high-density GM1 clusters that form in the liquid-ordered phase. These findings imply that multiple pathways exist in the plasma membrane to facilitate the rapid amplification and persistence of signals in a synergistic manner.

Dynamic phase behavior of freestanding model lipid bilayer membranes upon Sphingomyelinase reaction

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.