How can peripheral membrane proteins be removed?

Peripheral membrane proteins are typically associated with the lipid bilayer or with integral membrane proteins through ionic and hydrophilic interactions rather than being embedded within the membrane. Therefore, their removal generally requires disrupting these interactions rather than damaging the membrane itself.

Increasing salt concentration can lead to the disruption of ionic interactions that hold peripheral membrane proteins in place. Salt disrupts electrostatic attractions between charged groups in the protein and in the membrane or other components, thereby causing the protein to detach without compromising the structural integrity of the membrane.

Changing the pH can also be effective because it alters the charge state of the amino acid residues in the protein and possibly in the membrane, which might weaken the interactions that keep the peripheral membrane proteins bound.

In contrast, strong detergents are typically employed to solubilize integral membrane proteins and disrupt the membrane itself, which is not selective for peripheral proteins. Freezing the membrane may preserve its structure while not effectively affecting the interactions of peripheral proteins. Adding heat can denature proteins but may also damage the membrane structure itself. Thus, the method of increasing salt or adjusting the pH is the most appropriate choice for selectively removing peripheral membrane proteins.