They are water-soluble, with mostly hydrophilic surfaces. Many peripheral proteins adhere to exposed domains of integral proteins, by ionic and H-bond interactions. Some cytosolic proteins include domains that recognize and bind to polar head-groups of particular membrane lipids. PH domains mediate reversible binding of many signal proteins to the cytosolic surface of the plasma membrane. The kinases that catalyze transfer of phosphate from ATP to the inositol moiety of phosphatidylinositol, creating ligands recognized by PH domains, are themselves regulated by signal pathways.
Integral proteins have domains that extend into the hydrocarbon core of the membrane.
Integral proteins can be removed from membranes only by treatment with detergents , amphipathic molecules that break up the lipid bilayer. The hydrophobic domains of detergents substitute for lipids in coating hydrophobic surfaces of integral proteins. This allows the proteins to dissolve in water. Without detergents, purified integral proteins tend to aggregate, as their hydrophobic surfaces come together, to minimize contact with water. Such an anchor may allow reversible membrane association.