Membrane interaction and selectivity of novel alternating cationic lipid-nanodisc assembling polymers

Area of Science:

• Polymer Chemistry
• Biophysical Chemistry
• Materials Science

Background:

• Synthetic polymer nanodiscs are crucial tools for detergent-free solubilization and structural analysis of membrane proteins (MPs) in their native lipid environments.
• Amphipathic copolymers form water-soluble nanodiscs encapsulating phospholipids and MPs.

Purpose of the Study:

• To establish the nanodisc-forming ability of novel alternating copolymers of N-alkyl functionalized maleimide (AlkylM) and N-methyl-4-vinyl pyridinium iodide (MVP).
• To investigate how varying N-alkyl chain length in poly(MVP-co-AlkylM) affects nanodisc properties and membrane interactions.

Main Methods:

• Synthesis of alternating copolymers with systematic variations in N-alkyl chain length.
• Physicochemical techniques to characterize nanodisc size, structure, and lipid solubilization efficiency.
• Dye-release assays and native cell systems (bacterial and human red blood cells) to assess membrane selectivity.

Main Results:

• Lipid solubilization increased with N-alkyl chain length (methyl to n-butyl maleimide).
• More hydrophobic polymers formed smaller nanodiscs, influencing lipid ordering.
• Polymers with shorter N-alkyl chains showed selective disruption of bacterial membranes over human red blood cells, particularly poly(MVP-co-PM).

Conclusions:

• Polymer hydrophobicity is a key factor in tuning nanodisc size and membrane interaction selectivity.
• These findings provide a framework for designing polymers for selective membrane solubilization, biosensing, and antimicrobial development.
• The selective membrane disruption by specific polymer derivatives offers potential for targeted antimicrobial strategies.