Local Pressure Changes in Lipid Bilayers Due to Adsorption of Melittin and Magainin-h2 Antimicrobial Peptides: Results from Computer Simulations

Abstract

We performed a series of coarse-grained computer simulations in order to study how the placement of melittin and magainin-h2 antimicrobial peptides on the surface of the bilayer changes the local pressure profiles in the bilayer. The simulations were done using the NPT ensemble when the total stress on the bilayer was zero and also using the NP(z)AT ensemble, with a nonzero total stress. In the NPT ensemble, although the total stress was zero, each leaflet of the bilayer experienced a nonzero stress, and the stresses are equal by magnitude, but opposite in their direction. The observed stresses acting on the monolayers may cause the rupture of the monolayers to release the stress. Our simulations were done at different peptide to lipid ratio (P/L). When the P/L ratio was 1/50 there was no large difference in the local pressure profile for bilayers with melittin versus bilayers with magainin-h2. When simulations were performed in the NP(z)AT ensemble at P/L = 3/100 we observed a large difference in the pressure profiles in the bilayers with melittin peptides compared to the bilayer with magainin-h2. The observed in this case difference in stress may explain the difference in actions of melittin and magainin at high P/L.

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era

“…This transformation induces the segregation of hydrophilic/charged amino acids in space from the hydrophobic residues, which results in an amphipathic structure that is recognized as a prerequisite for AMPs to act on membranes . Electrostatic interactions between the positively charged residues of AMPs and negatively charged components of bacterial membranes have been widely reported to be the primary antimicrobial mechanism of most AMPs, including melittin, magainin, and cathelicidins, and the nonpolar face of those peptides can penetrate further into the membrane …”

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane

“…For example, under the actions of melittin, the distribution of membrane stress is changed notably. Considering that the structure of a lipid bilayer is planar, the membrane stress σ (σ outer or σ inner refers to the stress of the corresponding monolayer) can be calculated as follows: sans-serifσ=σouterZ+σinnerZ=−∫Z1Z0PZdz+∫Z2Z0PZdz PZ=PLZ−PNZ PLZ=Pxx+Pyy/2 where P L (Z) is the local lateral pressure depending on the Z-coordinate, P N (Z) is the local normal pressure, and Z 0 is the Z coordinate of the bilayer center, while Z 1 and Z 2 refer to positions outside of the two monolayers, respectively [84]. For an undisturbed lipid bilayer, the pressure distribution across the membrane is symmetric, that is, σ outer (Z) ≈ −σ inner (Z) or σ=0.…”

“…However, under the actions of the membrane-bound melittin, the symmetry of the pressure is broken. Goliaei et al drew the Z-dependent distribution profiles of membrane pressure both before and after peptide binding [84]; a hump appeared in the region corresponding to lipid tails of the outer monolayer (exactly the peptide binding site), while a decrease occurred simultaneously in the tail region of the inner monolayer. Quantitative analysis demonstrated that the stress of each monolayer changed differently, as σ outer = −6.4 ± 0.2 mN/m, σ inner =6.9 ± 0.8 mN/m (when P/L = 1/50) or σ outer = −8.8 ± 0.3 mN/m, σ inner = 9.4 ± 0.8 mN/m (when P/L = 1/33).…”

Opening of the Blood-Brain Barrier Tight Junction Due to Shock Wave Induced Bubble Collapse: A Molecular Dynamics Simulation Study

“…When the length and time scales of the processes are large in comparison with atomic scales one can use coarse grained (CG) simulations where, for example, a group of atoms is represented by an effective particle and the interaction between atoms is reduced to interaction between these kinds of effective particles, as it is done in the force field called MARTINI 20 . Initially constructed to 3 describe model lipid membranes, MARTINI was extended to describe interactions between membranes and proteins 21 , often producing a successful nanoscopic description of the processes taking place in these systems 22 We used MARTINI to study interactions of antimicrobial peptides, such as melittin and/or magainin, with lipid membranes [23][24][25] . Very recently we also used MARTINI to study shock wave induced implosions of bubbles situated next to lipid bilayers and the damage to bilayers due to such implosions [26][27][28] .…”