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

Abstract

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.

Transcription-Factor-Induced Aggregation of Biomimetic Oligonucleotide-b-Protein Micelles

“…Recently, the group of Qian and Yang conjugated several commercially available azido-terminated ON sequences (of 21 to 38 bases) to a short commercial hydrophobic ELP with the VPGFG sequence (MW = 476 g/mol) modified at the C -terminus by an aliphatic alkyne group. , A copper­(I)-catalyzed azide–alkyne cycloaddition reaction in water/DMSO mixtures afforded the diblock bioconjugates, which were extracted by excision of the electrophoresed SDS-PAGE gels. In their first work, amphiphilic (VPGFG) 6 - b -ON and (VPGFG) 6 - b -complementary ON bioconjugates (ON from 21 to 38 bases) were hybridized together and formed 55–60 nm diameter vesicles.…”

“…10 The vesicles encapsulated hydrophobic molecules (Nile red, doxorubicin), opening the way for potential drug delivery applications. Building upon this success, 36 they next investigated the influence of the ELP molar mass and the nature of the ON on the (VPGFG) y -b-ON x temperature and morphology transitions. While (VPGFG) 6 -b-ON 32 presented a CMT of 25 °C and the (VPGFG) 5 -b-ON 32 at 33 °C, the shorter block (VPGFG) 4 -b-ON 32 did not show any phase transition, highlighting the importance of a significant hydrophobic block to stabilize the vesicles.…”

The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair

“…As a thermoresponsive peptide, ELPs can self-assemble into different nanostructures by adjusting the composition of the peptide chain structure, including micelles [31][32][33], vesicles [25,[34][35][36] and nanofibers [37,38].…”