SDS-PAGE vs Native PAGE: Key Differences Explained
SDS-PAGE adds detergent to unfold proteins into linear chains and separates by mass alone; Native PAGE keeps proteins in their folded, active state and separates by both size and charge.
Students reach for SDS-PAGE when they “just want to see a band,” but when an assay shows zero activity afterwards, they panic and rerun the same sample on a Native gel—realizing too late that shape matters.
Key Differences
SDS-PAGE: SDS denatures, uniform negative charge, migration = log(MW). Native PAGE: no SDS, proteins keep charge & shape, migration = f(size, charge, conformation). Buffers, stains, and power settings differ.
Which One Should You Choose?
Need purity check or MW? Pick SDS-PAGE. Need activity, complex integrity, or binding partners? Go Native PAGE. Many labs run both—SDS first for clarity, Native second for function.
Can I use the same gel recipe?
No. SDS gels need SDS in buffers; omit it for Native gels and adjust pH for protein stability.
Why did my Native gel show no bands?
Proteins may be insoluble or have net zero charge at the running pH; tweak buffer or add mild detergent.