Proline isomerization regulates the phase behavior of elastin-like polypeptides in water

Responsiveness of proteins and polymers in aqueous solutions plays an important role in biomedical applications and in designing the advanced functional materials. A well-known class of synthetic intrinsically disordered proteins (IDPs) is that of elastin-like polypeptides (ELPs), which exhibits a lower critical solution temperature (LCST) behavior in pure water. Here, we study and compare the influence of the cis/trans proline isomerization on the phase behavior of ELPs in dilute aqueous solution. Our results reveal that cis isomers play an important role in tuning the phase behavior of ELPs by hindering the peptide-water hydrogen bonding while promoting intramolecular interactions. In particular, an ELP with all proline residues in cis state remains collapsed without any noticeable LCST-like behavior as temperature increases, while showing a first-order-like LCST transition if all proline residues are in trans state.