How do semipermeable membranes separate proteins of different sizes?

Semipermeable membranes separate proteins of different sizes primarily through the process of diffusion based on the physical dimensions of the membrane's pores.1

When a solution containing a mixture of proteins is separated from a solvent (such as water) by a porous membrane, the membrane acts as a physical barrier. The separation occurs because:1

• Size Exclusion: Smaller molecules or proteins are able to pass freely through the pores of the membrane, while larger protein molecules are too bulky to fit through and are thus retained.12
• Differential Diffusion: Proteins that are close in size to the diameter of the pores may be able to pass through, but they do so more slowly than smaller molecules, as they must "squeeze" through the openings.1
• Time Dependency: Because this is a rate-based separation process, the extent of the separation is dependent on the amount of time allowed for diffusion to occur.1

Techniques such as dialysis utilize this principle to remove smaller dissolved salts or molecules from solutions containing larger proteins.32