Small Molecules as Modulators to Prevent Mucin Aggregation via Delaying Liquid-to-Solid Phase Transition.

Area of Science:

• Biochemistry
• Molecular Biology
• Pathophysiology

Background:

• Aberrant mucin aggregation is implicated in various mucosal disorders.
• The molecular mechanisms driving mucin aggregation under physiological conditions are not fully understood.
• Mucin solubility is sensitive to calcium concentration, pH, and macromolecular crowding.

Purpose of the Study:

• To investigate the molecular determinants of mucin aggregation under physiologically relevant conditions.
• To evaluate the inhibitory effects of Scopolamine (SCP), Quercetin (QUE), and Epigallocatechin-3-gallate (EPGG) on mucin aggregation.
• To elucidate the mechanisms by which these bioactive compounds modulate mucin aggregation.

Main Methods:

• Systematic investigation of mucin aggregation under various stressors.
• Evaluation of the concentration and time-dependent effects of SCP, QUE, and EPGG.
• Analysis of condensate morphology and internal molecular dynamics.
• Permeability profiling of bioactive compounds.

Main Results:

• All three tested bioactives (SCP, QUE, EPGG) suppressed mucin aggregation in a concentration- and time-dependent manner.
• SCP demonstrated efficacy via electrostatic competition under acidic conditions.
• QUE and EPGG inhibited aggregation through hydrogen bonding and hydrophobic interactions.
• Bioactives reduced internal molecular dynamics without altering condensate morphology.
• SCP was identified as a systemically accessible modulator.

Conclusions:

• Bioactive compounds can effectively suppress aberrant mucin aggregation.
• Distinct mechanisms of action were identified for SCP, QUE, and EPGG.
• Small-molecule bioactives represent promising therapeutic agents for mucin-associated pathologies.
• SCP shows potential as a systemically administrable therapeutic modulator.