Bilayer-couple model of OMV formation in P. aeruginosa. The model proposes that PQS induces OMV formation through a mechanism of asymmetric expansion of the outer leaflet of the outer membrane. (A) Whether PQS is added exogenously or exported from the producing cell, the hydrophobic nature of PQS causes it to associate with LPS, where it makes specific contacts with the 4′-phosphate and acyl chains of lipid A. (B) These specific interactions contribute to a low rate of flip-flop between leaflets, causing PQS to expand the outer leaflet relative to the inner leaflet. When the ratio of the leaflet areas becomes sufficiently large, the membrane as a whole is forced to buckle in response to this asymmetry. (C) With continuing insertion of PQS, curvature increases until OMVs, which can accommodate a large ratio of outer to inner leaflet area, bud from the surface. Red, PQS; green, LPS; yellow, phospholipids. Polysaccharides have been omitted from LPS for clarity.