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The passive membrane permeation of small-molecule drugs and relatively small hydrophobic peptides is relatively well understood. In contrast, how long polar peptides can directly pass through a membrane has remained a mystery. This process can be achieved with transcellular permeation enhancers, contributing significantly to the oral transcellular absorption of important peptide drugs like semaglutide — the active component in Ozempic, which is used as Rybelsus in a successful oral formulation. Here we now provide, for the first time, a detailed, plausible molecular mechanism of how such a polar peptide can realistically pass through a membrane paired with the permeation enhancer salcaprozate sodium (SNAC). We provide not only simulation results, obtained with scalable continuous constant pH molecular dynamics (CpHMD) simulations, but also experimental evidence (NMR, DOSY, and DLS) to support this unique passive permeation mechanism. Our computational and experimental evidence points toward the formation of permeation-enhancer-filled, fluid membrane defects, in which the polar peptide can be submerged in a process analogous to sinking in quicksand.