Modeling cell membrane perturbation by molecules designed for transmembrane electron transfer.

Area of Science:

• Biophysics
• Materials Science
• Computational Chemistry

Background:

• Conjugated oligoelectrolytes (COEs) enhance biological charge transfer, impacting bioelectrochemical systems.
• Understanding COE interaction with cell membranes at a molecular level is crucial for their application.
• Current knowledge lacks detailed insights into how COEs perturb biological membranes.

Purpose of the Study:

• To investigate how COEs perturb cell membranes.
• To correlate COE structural features (aromatic rings, fluorine substitution) with membrane interaction.
• To understand the molecular mechanisms of COE-induced membrane deformation.

Main Methods:

• Molecular dynamics (MD) simulations to model COE-membrane interactions.
• Atomic force microscopy (AFM) to visualize membrane morphology changes.
• Toxicity testing (minimum inhibitory concentration - MIC) to assess biological impact.

Main Results:

• All investigated COEs caused membrane thinning by drawing lipid phosphate heads towards the bilayer center.
• The four-ringed COE caused minimal deformation and disruption (MIC = 64 μmol L⁻¹).
• Three-ringed COEs induced significant thinning (<3.0 nm) and pitting, especially unfluorinated versions.
• Fluorination of three-ringed COEs delocalized thinning and reduced toxicity (MIC = 4 μmol L⁻¹ vs 2 μmol L⁻¹).

Conclusions:

• COE structure dictates the extent of cell membrane perturbation.
• Membrane thinning and pitting are key mechanisms of COE-induced disruption.
• Fluorine substitution can mitigate membrane perturbation and toxicity through hydrophobic polar interactions.
• This study provides a foundation for designing COEs with controlled membrane interactions for biomedical applications.