Polystyrene nanoplastics modulate VGLL3 phase separation by enhancing intermolecular interactions: Implications for...

Area of Science:

• Environmental Science
• Biochemistry
• Materials Science

Background:

• Microplastics and nanoplastics (MNPs) are pervasive pollutants with potential health implications.
• The effect of MNPs on protein liquid-liquid phase separation (LLPS), crucial for cellular regulation and implicated in fibrosis, is largely unknown.
• Vestigial-like family member 3 (VGLL3) is a transcriptional cofactor involved in fibrosis.

Purpose of the Study:

• To investigate the impact of polystyrene nanoparticles (PS NPs) with varying surface chemistries and sizes on the phase behavior of VGLL3.
• To elucidate the mechanisms by which MNPs might influence protein LLPS relevant to fibrotic diseases.

Main Methods:

• Investigated VGLL3 LLPS induction by PS NPs with carboxyl (-COOH), amine (-NH₂), and bare surfaces using varying concentrations and sizes.
• Characterized the dynamic and reversible nature of VGLL3 condensates using 1,6-hexanediol.
• Utilized dynamic light scattering (DLS) to analyze NP-protein complex formation.
• Employed molecular docking to model interactions between PS-COOH NPs and VGLL3.

Main Results:

• PS-COOH NPs robustly and selectively induced VGLL3 LLPS in a concentration- and size-dependent manner.
• Re-entrant dissolution of VGLL3 condensates was observed at higher PS-COOH NP fractions.
• PS NPs and PS-NH₂ NPs showed minimal effects on VGLL3 LLPS.
• Molecular docking suggested a scaffold model where PS-COOH NP surfaces mediate VGLL3 multivalent interactions.

Conclusions:

• Carboxylate-rich MNPs can modulate the phase behavior of VGLL3, a key regulator in fibrosis.
• This study provides a mechanistic understanding of how specific MNP surface chemistries can alter protein condensates.
• Findings offer a framework for assessing MNP-associated health risks and designing safer nanomaterials.