Environments. Individually, SNAC aggregation in aqueous media has been reported. However, SNAC's behavior in non-polar environments is still mostly unknown yet crucial for facilitating the membrane permeation of semaglutide. Our observations now reveal that protonated SNAC also has the potential to aggregate in non-polar environments, as demonstrated by DLS (Fig. ) and through CpHMD simulations (Fig. ). Specifically, the CpHMD simulations show Colston, Faivre, and Schneebeli* ______________________________________________________________________________ 9 SNAC forming dynamic aggregates in CH₂Cl₂ (Fig. ) as well as inside a model membrane (Figs. ). The computational model indicates that SNAC aggregation is driven by hydrogen bonding (Fig. and Supplementary Fig. ), including branched hydrogen bonds that can lead to dynamic network formation inside the membrane.