Secondary Structure-Governed Phase Separation Behavior in Glutamate-Based Polypeptides

The phase separation behavior ofbiomacromolecules playsa keyrole in the fields of biology and medicine. In this work, we gaina deep insight into how the primary and secondary structures governand regulate the phase separation behavior of polypeptides. To thisend, we synthesized a series of polypeptides with tailorable hydroxyl-containingside chains. The secondary structure of polypeptides can be modulatedby the local chemical environment and content of side chains. Interestingly,these polypeptides with different helical contents exhibited uppercritical solution temperature behavior with marked differences inthe cloud point temperature (T (cp)) andthe width of hysteresis. The phase transition temperature is highlyrelevant to the content of secondary structure and interchain interactionsof polypeptides. The aggregation/deaggregation and the transitionof secondary structure are completely reversible during heating-coolingcycles. Much to our surprise, the recovery rate of the alpha-helicalstructure governs the width of hysteresis. This work establishes thestructure-property relationship between the secondary structureand phase separation behavior of the polypeptide and delivers newinsight into the rational design of peptide-based materials with tailor-madephase separation behavior.

Automated summary

In this study, the phase separation behavior of polypeptides was investigated by synthesizing a series of polypeptides with tailorable hydroxyl-containing side chains. It was found that the secondary structure of polypeptides can be modulated by the local chemical environment and content of side chains. The different helical contents of these polypeptides exhibited marked differences in the cloud point temperature and the width of hysteresis. The recovery rate of the alpha-helical structure was found to govern the width of hysteresis.