Fig. 4: Supermeres are enriched in shed membrane proteins.

a, Heatmap of normalized spectral counts of APP and other select membrane proteins involved in Alzheimer’s disease. b, Immunoblot analysis of APP in the whole-cell lysate, sEV-P as well as exomeres and supermeres of DiFi cells using N-terminal (left) and C-terminal (right) APP antibodies. c, C-terminal APP fragment; i, immature APP; m, mature APP; and s, soluble APP. c, FAVS analysis of APP in the sEV-P (left), exomeres (middle) and supermeres (right) of DiFi cells. d, Immunoblot analysis of MET in SC cells and corresponding extracellular samples using both N-terminal (left) and C-terminal (right) MET antibodies. c, C-terminal MET fragment; p, pro-form MET; m, mature MET; s, soluble MET. e, FAVS analysis of MET in the DiFi sEV-P, exomeres and supermeres using MET antibody directly conjugated to Alexa Fluor-647. f, Immunoblot analysis of GPC1 in the whole-cell lysate, sEV-P, exomeres and supermeres derived from PANC-1 (left) and HREC (right) cells using a rabbit monoclonal antibody. g, FAVS analysis of GPC1 in the sEV-P (left), exomeres (middle) and supermeres (right) of DiFi cells. h, Immunoblot analysis of CEA in whole-cell lysates, sEV-Ps, exomeres and supermeres derived from DiFi (top left), LS174T (top right), LIM1215 (bottom right) and Calu-3 (bottom left) cells. i, Immunoblot analysis of CEA in the sEV-Ps, exomeres and supermeres isolated from control individuals (NL) and plasma from patients with CRC. c,e,g, The red boxes indicate APP-, GPC-1- or MET-positive particles, respectively. The percentages indicate the percent of particles that contain APP, GPC-1 or MET, respectively, above the detection limit. b,d,f,h,i, Equal quantities (30 µg) of protein from each fraction were analysed. Exom, exomere; super, supermere; WCL, whole-cell lysate.