In order to understand how the material properties of lipid bilayers could affect integral membrane protein function, we examined the effect of a hydrophobic mismatch on the structure and function of membrane-spanning gramicidin channels. Changes in lipid bilayer thickness affect the conformational preference of membrane-spanning gramicidin A (gA) channels (single-stranded [SS] dimers <-> double-stranded [DS] diners) and induces an additional conductance state in the standard (SS) beta(6.3)-helical channel. These results provide experimental evidence for the importance of energetic coupling between the bilayer and imbedded inclusions. (C) 1997 Federation of European Biochemical Societies.