Side-Functionalization of Poly(<scp>l</scp>-methionine) for Ice Control

Controlling ice growth is crucial during the cryopreservation of cells, but the current application of small molecules as cryoprotectants still remains a challenge. Inspired by structures of natural antifreeze (glyco)proteins, in this work, functionalized poly(l-methionine)s (PMets) are synthesized with different side groups including hydroxyl, threonine-mimetic with both methyl and hydroxyl groups (PMet-MOH), zwitterion with carboxyl and sulfonium (PMet-COOH), glycerol, and trehalose pendants. Results suggest that these functionalized PMets tend to self-assemble into 100-300 nm nanoparticles with positive charges in water. The functional structures have a remarkable influence on their ice control properties. It is supposed that PMet-MOH inhibits ice growth possibly through the adsorption mechanism by adjacent methyl and hydroxyl groups, whereas trehalose-tethered PMet can restrict diffusion of water molecules with the strongest ice recrystallization inhibition activity and zwitterionic PMet-COOH promotes ice nucleation obviously. This work offers valuable insight into the development of functional polypeptides as promising biocompatible cryoprotectants.