Peptide‐Induced Division of Polymersomes for Biomimetic Compartmentalization

Polymersomes are synthetic vesicles that mimic the architecture of cellular compartments such as the cell membrane and organelles. These biomimetic compartments facilitate the creation of cell‐like chemical systems, including microreactors and synthetic organelles. However, the construction of hierarchical multi‐compartment systems remains challenging and typically requires the encapsulation of pre‐formed vesicles within a host compartment. Here, we report the formation of multicompartment polymersomes with a vesicle‐in‐vesicle architecture achieved through self‐division induced by short peptides incorporated into the vesicle membrane. A phenylalanine‐phenylalanine‐methionine (FFM) tripeptide was designed and encapsulated into the polymersome via microfluidics. We demonstrate that vesicle self‐division occurs due to peptide incorporation into the membrane in response to pH changes. This self‐division creates internal vesicles capable of colocalizing enzymes. The hybrid polymer‐peptide system described here provides a straightforward method for developing subcompartmentalized systems, paving the way for engineering microreactors with life‐like properties. Polymersomes, synthetic vesicles mimicking cellular compartments, enable the creation of cell‐like chemical systems such as microreactors and synthetic organelles. We report multicompartment polymersomes with a vesicle‐in‐vesicle architecture formed through self‐division, driven by the pH‐triggered incorporation of a phenylalanine‐phenylalanine‐methionine tripeptide into the membrane. This process produces internal vesicles that colocalize enzymes, offering a method for engineering adaptive microreactors.