Protein Cage-like Vesicles Fabricated via Polymerization-Induced Microphase Separation of Amphiphilic Diblock Copolymers

Highly symmetric protein cages represent one of the most artistic architectures formed by biomolecules. However, the underlying reasons for the formation of some of these architectures remain unknown. The present study aims to investigate the significance behind their morphological formation by fabricating protein cage-like vesicles using a synthetic polymer. The vesicles were synthesized by combining polymerization-induced self-assembly (PISA) with polymerization-induced microphase separation (PIMS), employing an amphiphilic poly(methacrylic acid)-<i>block</i>-poly(<i>n</i>-butyl methacrylate-<i>random</i>-cyclohexyl methacrylate-<i>random</i>-methacrylic acid) diblock copolymer, PMAA-<i>b</i>-P(BMA-<i>r</i>-CMA-<i>r</i>-MAA). The copolymer, with a 60 mol% molar ratio of CMA to the BMA units, produced clathrin-like vesicles with angular windows in their shell, resulting from the segregation of the hard CMA units from the soft BMA matrix in the hydrophobic phase of the vesicle. These vesicles were highly stable against rising temperatures. In contrast, the vesicles with a 30 mol% CMA ratio dissociated upon heating to 50 °C into triskelion-like segments due to intramolecular microphase separation. These findings indicate that designing synthetic polymers can mimic living organ morphologies, aiding in elucidating their morphological significance and inspiring the development of new materials utilizing these morphologies.