Abstract
We investigate the interactions between lipid bilayers and amphiphilic peptides using a solvent-free coarse-grained simulation technique. In our model, each lipid is represented by one hydrophilic and three hydrophobic beads. The amphiphilic peptide is modeled as a hydrophobic-hydrophilic cylinder with hydrophilic caps. We find that with increasing peptide-lipid attraction the preferred state of the peptide changes from desorbed, to adsorbed, to inserted. A single peptide with weak attraction binds on the bilayer surface, while one with strong attraction spontaneously inserts into the bilayer. We show how several peptides, which individually bind only to the bilayer surface, cooperatively insert. Furthermore, hydrophilic strips along the peptide cylinder induce the formation of multipeptide pores, whose size and morphology depend on the peptides’ overall hydrophilicity, the distribution of hydrophilic residues, and the peptide-peptide interactions. Strongly hydrophilic peptides insert less readily, but prove to be more destructive to bilayer integrity.
Highlights
The interaction between biological membranes and many naturally produced peptides, such as gene-encoded antimicrobial peptides (APs) and toxins, have been extensively studied for the last few decades
Numerous APs have been isolated from different multicellular organisms, for instance the magainin family of the African frog Xenopus laevis [1,2], melittin [3], and alamethicin of the fungus Trichoderma viridae [4]
Besides a sufficiently strong lipidpeptide attraction, the presence of hydrophilic caps at both ends is necessary to rearrange the lipids into a structure that facilitates the transmembrane peptide insertion
Summary
The interaction between biological membranes and many naturally produced peptides, such as gene-encoded antimicrobial peptides (APs) and toxins, have been extensively studied for the last few decades. While significant progress has been made concerning molecular modeling of AP adsorption onto and insertion into a bilayer [20], the known cooperative nature of their action implies that the interplay of many such peptides needs to be studied to understand the origin of their cytotoxicity For computational feasibility this cannot be accomplished on the atomistic level, various coarse-grained simulational approaches have recently been undertaken [21,22,23,24,25,26]. In the absence of explicitly modeled solvent, suitable cohesive interactions between the tails robustly induce self-assembly into fluid bilayer membranes over a wide range of few tuning parameters (see [31] for a recent review on solvent-free membrane simulation approaches) Their large-scale properties faithfully reflect those of real lipid bilayers [30,32,33]. Since for our work it is exclusively the long time regime that is physically relevant, we will always include the speedup ft ’ 1500 when mapping timescales
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