Ordered-disordered domain coexistence in ternary lipid monolayers activates sphingomyelinase by clearing ceramide from the active phase

► SMase activity is favored by the presence of liquid-ordered domains. ► Fluorescent-labeled SMase adsorbs preferentially to the liquid-expanded phase. ► Cer production occurs mainly in the liquid-expanded phase, rather than at domain borders. ► The SMase-driven changes of surface structure depend on the liq-expanded/liq-ordered proportion. ► The modulation mechanism involves substrate supply and low product in the active phase.