This work identifies signals structurally encoded in soluble cytosolic proteins that induce an intricate or simple spanning of the inner membrane in a cellular compartment. Such signals are defined by the extent of intramolecular desolvation of backbone hydrogen bonds, a determinant factor in the interactivity of soluble proteins. The protein scaffolding of inner membranes varies widely but such differences do not explain a priori whether the membrane spanning will be simple or intricate. To address this problem, we show that a fluid phospholipid bilayer confining a water compartment for a soluble protein at 38 muM concentration is drawn to increase its interface area proportionally with the extent of intramolecular under-desolvation of the protein structure. We also predict and measure the optimal interface surface tension that enables such phenomenology. The in vitro kinetics of interface morphology development is autocatalytic, with an inhibitory mechanism switching on as the local concentration of protein molecules adsorbed on the bilayer reaches a threshold. (C) 2003 American Institute of Physics.