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Chiral Matching between Nucleic Acids and Polypeptides Facilitates Liquid-Liquid Phase Separation.

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This study reveals how liquid-liquid phase separation (LLPS) evolves from single molecules to large condensates, driven by matching chirality. This finding offers new ways to control LLPS for medicine and biomaterials.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Biomaterials Science

Background:

  • Liquid-liquid phase separation (LLPS) is a crucial cellular process.
  • The full mechanism of LLPS evolution, from intramolecular to intermolecular interactions, remains unclear.

Purpose of the Study:

  • To investigate the evolution mechanism of LLPS using poly(G-quadruplex) and poly(lysine).
  • To elucidate the role of chirality in LLPS formation and progression.

Main Methods:

  • Single-molecule force spectroscopy with optical tweezers to study intramolecular condensation.
  • Microscopy-based ensemble clouding assay to analyze macroscopic condensate properties.

Main Results:

  • Identified four intramolecular condensation states at low concentrations.
  • Observed LLPS evolution from liquid-like to solid-like condensates with increasing concentrations.
  • Demonstrated that matching chirality between nucleic acids and peptides facilitates LLPS.

Conclusions:

  • Intermolecular interaction, driven by matching chirality, is the primary force in LLPS.
  • Understanding LLPS evolution opens avenues for targeted therapeutics and functional biomaterials development.