How does sodium dodecyl sulfate help separate proteins by size?

In the context of analytical chemistry, sodium dodecyl sulfate (SDS) is essential for separating proteins by size during gel electrophoresis.

Under normal conditions, proteins have varying shapes and intrinsic charges, which would prevent them from being separated solely by size in an electric field. To overcome this, the protein sample is treated with SDS, a detergent that performs two critical functions:

• Denaturation: SDS destroys the protein's higher-order structural features, ensuring that all proteins are unfolded into a similar linear shape.1
• Uniform Charge: The detergent binds to the protein, coating it with a negative charge that is proportional to its length. This gives all resulting SDS-protein complexes a uniform charge density.1

Because the proteins now share the same shape and charge-to-mass ratio, they migrate through the porous gel matrix based exclusively on their molecular size. In this setup, smaller proteins encounter less resistance and migrate more quickly through the pores, while larger, heavier proteins move more slowly, allowing for effective size-based resolution.21