pH-dependent peptide aggregation and translocation across octanol and hexane interfaces: insights from umbrella...

Area of Science:

• Biochemistry
• Membrane Biophysics
• Drug Delivery Systems

Background:

• pH-dependent peptides exhibit membrane-permeabilizing properties, forming pores at acidic pH.
• The aggregation and translocation mechanisms of these peptides across cell membranes remain poorly understood.

Purpose of the Study:

• To investigate the aggregation and translocation pathways of pHD24 peptides at acidic (pH 4) and physiological (pH 7) conditions.
• To compare peptide activity at octanol-water and hexane-water interfaces, which mimic phospholipid bilayers.
• To elucidate the role of pH in peptide aggregation and membrane interaction.

Main Methods:

• Utilized octanol-water and hexane-water interfaces as biomembrane models.
• Studied peptide aggregation and translocation at pH 4 and pH 7.
• Analyzed peptide-peptide interactions, including hydrogen bonding and electrostatic forces.

Main Results:

• pHD24 peptides demonstrated enhanced aggregation and translocation at acidic pH (pH 4) compared to physiological pH (pH 7).
• Translocation at the octanol-water interface occurred via a water channel with a calculated energy barrier.
• Favorable peptide-peptide interactions at acidic pH promoted aggregation and larger pore formation.

Conclusions:

• Acidic pH significantly facilitates the aggregation and translocation of pHD peptides across biomimetic membranes.
• Understanding these mechanisms provides insights for designing synthetic peptides for targeted drug delivery.
• The study highlights the importance of pH in modulating peptide-membrane interactions.