Dipeptides Embedded in a Lipid Bilayer Membrane as Synthetic Water Channels

Abstract

Water channels are essential to life sciences and many biological processes. We report a molecular simulation study on dipeptides embedded in a lipid (dipalmitoylphosphatidylcholine) membrane as synthetic water channels. Five dipeptides are examined including FF, FL, LF, and LL (with hydrophilic channels) and AV (with hydrophobic channel). It is found that AV is unstable in the lipid membrane due to incompatible interaction between the hydrophilic external surface of AV and the hydrophobic lipid tails; whereas FF, FL, LF, and LL with hydrophobic external surface exhibit good stability. In the four hydrophilic channels FF, FL, LF, and LL, water chains are formed; the number of chains ranges from multiple, two to one depending on channel diameter; moreover, water undergoes single-file diffusion and the mobility is enhanced with increasing channel diameter. The permeation rate of water in the FF channel is 9.20/ns, about three times that in aquaporin; however, the rate in FL, LF, and LL is much slower. Intriguingly, the rate can be tuned by a lateral stress/strain on the lipid membrane. The simulation study provides fundamental understanding on the stability of dipeptide channels embedded in a lipid membrane, quantitatively characterizing water structure, dynamics, and permeation in the channels. These microscopic insights are useful for the development of new water channels.

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

“…Altogether, these site-specific peptide probes enabled us to view water penetration into the hydrophobic region of the bilayer, which may be otherwise thermodynamically unfavorable in peptide-free bilayers. Previous literature has observed negligible water presence beyond the ester carbonyl in pure lipid membranes (75)(76)(77) and has also suggested that embedded amino acids and peptides may facilitate water diffusion across lipid bilayers and into the alkyl bulk (6,(78)(79)(80)(81)(82). Our results are consistent with this literature; however, additional methods beyond the scope of this study are required to rule out potential peptide multimers in the membrane.…”

Simulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetration

“…Our results could possibly explain the earlier stages of water permeability findings of antimicrobial peptides that favor water penetration in bacterial membranes even at very low peptide concentrations, without destroying the membrane integrity. 92–95 However, simulations with higher peptide concentrations and larger membranes should be performed to confirm the positive correlation between peptide concentration and water flow and concentration within membranes.…”

The coming of age of water channels for separation membranes: from biological to biomimetic to synthetic

“…116 Another study has also hypothesized that the permeability of biomimetic dipeptide channels can be affected by the lateral stress and strain forces on the lipid membrane. 117 It is obvious that the assimilation of water channels into membranes can induce structural changes in the lipid bilayer and the consequential water transport pathway through the latter. We recommend future studies to resolve the intricate interplay between channels and the lipid bilayer because the permselectivity of such unique membrane designs remains to be resolved by experimental studies.…”