Dynamic Compartmentalization of Peptide-Oligonucleotide Conjugates with Reversible Nanovesicle-Microdroplet Phase Transition Behaviors

Developing artificial microsystems based on liquid-liquid phase separation (LLPS) to mimic cellular dynamic compartmentalization has gained increasing attention. However, limitations including complicated components and laborious fabrication techniques have hindered their development. Herein, we describe a new single-component dynamic compartmentalization system using peptide-oligonucleotide conjugates (POCs) produced from short elastin-like polypeptides (sELPs) and oligonucleotides (ONs), which can perform thermoreversible phase transition between a nanovesicle and a microdroplet. The phase transition of sELP-ONs is thoroughly investigated, of which the transition temperature can be controlled by concentration, length of sELPs and ONs, base sequences, and salt. Moreover, the sELP-ON microcompartment can enrich a variety of functional molecules including small molecules, polysaccharides, proteins, and nucleic acids. Two sELP-ON compartments are used as nano- and microreactors for enzymatic reactions, separately, in which chemical activities are successfully regulated under different-scaled confinement effects, demonstrating their broad potential application in matter exchange and artificial cells.