Three possible models to explain how OMVs form in response to different stimuli. A) The accumulation of misfolded or overexpressed protein in the periplasm may result in a physical force on the outer membrane, causing the envelope to separate, the outer membrane to bulge, and eventually lead to the release of the OMV. B) External agents that act at the outer membrane could intercalate into the outer membrane, and disturb the packing of the outermost membrane. This disruption may lead to a change in the curvature of the membrane generating a bulge that eventually could bud off completely. C) A naturally secreted small molecule which can pass through the cell envelope could result in a change in the regulation of genes, causing an increase or decrease in levels of OMVs.