Protein Folding Landscapes in the Living Cell

This Perspective highlights studies of protein structure, stability, and folding kinetics that can now be carried out in prokaryotic and eukaryotic cells. The general features of cooperative folding transitions and kinetics remain the same as those in vitro, but the folding free-energy landscape and local viscosity vary according to microenvironments in the cellular landscape. Experiments in vitro provide a basis for comparing crowding and chemical effects with experiments inside of the cell. Perhaps cells even evolved to post-translationally modulate protein folding and binding through chemical patterns or by crowding.