Authors
Pravin Pokhrel, Zhilei Zhang, Jiahao Ji, Sajan Shakya, Jaren Jenyk, Alyssa Lower, Maxwell Janssen, Hanbin Mao
Published in
The journal of physical chemistry letters. Pages 9545-9552. Sep 04, 2025. Epub Sep 04, 2025.
Abstract
Liquid-liquid phase separation (LLPS) is a newly discovered phenomenon to modulate a multitude of cellular functions. Despite its importance, the full evolution mechanism of LLPS starting from intramolecular interactions to intermolecular condensations has yet to be revealed. In this study, we investigated a representative LLPS formed between negatively charged nucleic acids poly(G-quadruplex) and positively charged peptides poly(lysine). Harnessing the chiral nature of these two components, we elucidated an exquisite chirality effect on the LLPS formation using optical-tweezer-based single-molecule force spectroscopy, which revealed four states of intramolecular condensation at low component concentrations, and a microscopy-based ensemble clouding assay, which, in a complementary manner, discloses the shape and density of macroscopic intermolecular condensates at higher concentrations. We found that, with increasing concentrations, intramolecular interactions evolve to intermolecular condensations, resulting in liquid-like condensates followed by solid-like droplets. The entire evolution was facilitated by the matching chirality between poly(G-quadruplex) and poly(lysine), which confirmed that the intermolecular interaction is the driving force for the LLPS process. The elucidation of the full LLPS evolution offers ample opportunities to interfere with the LLPS process via chirality factors, which provides new avenues for targeted therapeutics and development of functional biomaterials.
PMID:
40906967
Bibliographic data and abstract were imported from PubMed on 05 Sep 2025.
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