Biomechanical Investigation of Bacterial Biofilm Membrane and Assessment of the Anti-Biofilm Peptide Effects on Molecular and Biomechanical Characteristics of the Membrane: A Molecular Dynamics Investigation

Ebrahimi Tarki, Fatemeh; Zarrabi, Mahboobeh; Sharbatdar, Mahkame; Abdi Ali, Ahya

Biomechanical Investigation of Bacterial Biofilm Membrane and Assessment of the Anti-Biofilm Peptide Effects on Molecular and Biomechanical Characteristics of the Membrane: A Molecular Dynamics Investigation

Document Type : Research Paper

Authors

Fatemeh Ebrahimi Tarki ¹

Mahboobeh Zarrabi ¹

Mahkame Sharbatdar ²

Ahya Abdi Ali ³

¹ Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran

² Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran

³ Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran

Abstract

Biofilms are complex bacterial aggregates surrounded by an extracellular matrix. Bacteria in the biofilm state show a 1000-fold increase in antibiotic resistance. This study explores new strategies involving antimicrobial peptides as an alternative to conventional antibiotics. Two approaches have been investigated for the anti-biofilm effects of peptides: inhibition of ppGpp signaling, which is crucial in biofilm development and persistence, and disruption of target cell membrane structure. Lipid bilayers have been prepared for biofilm state with lipid content close to reality based on experimental results and lipid bilayer model (POPE: POPG 2:1) and with all-atom molecular dynamics simulation, biomechanical and molecular characteristics have been assessed. The parameters of area per lipid, thickness, order, curvature, electron and mass density profiles, radial distribution function, compressibility, bending modulus, and interdigitation were calculated. The behavior of GL13K peptide in the presence of model and biofilm lipid bilayers was investigated, focusing on structural features, interaction energies, and accessible surface area. Unsaturated and cyclic-containing side-chain lipids in the biofilm bilayer led to a decrease in thickness and lateral diffusion, an increase in interdigitation and compressibility, bending modulus, and area per lipid compared to the model bilayer. In both cases, the presence of the peptide has increased membrane disorder. The peptide exhibited varying orientations and proximities, resulting in a higher accessible surface area when interacting with the model bilayer compared to the biofilm state.

Keywords

Antibiofilm peptides

Bacterial biofilm

Biomechanics

Molecular dynamics

Subjects