Chemistry of Materials
Communication
coefficient is directly proportional to the partition coefficient of
water between the membrane phase and aqueous solution, and
also to the diffusion constant of water within the membrane
phase.30 Triazole group is known to interact with biological
molecules through hydrogen bonding and dipole interactions,31
thus we propose that due to these capabilities, the 1,4 triazole
moiety enhances the water partition coefficient relative to
GMGTPC. We also propose that 1,4 triazole rings perturb lipid
packing, thus decreasing the mechanical strength. Interestingly,
when we doped the ATL1 membrane with 30 mol %
GMGTPC, a 36% increase in stretching modulus was observed.
The cohesive energy of the tetraether lipid incorporating the
1,4 triazole groups was 0.018 mJ/m2, which is a factor of 7.0
0.2 lower than GMGTPC and low compared to natural
phospholipids (0.05 to 0.5 mJ/m2).32 On a per-molecule basis,
these energy densities are very close to thermal energy. Thus,
thermal fluctuations should cause significant variations in
density and increase in local lateral compressibility, which all
would enhance the diffusion of water through the membrane
and lower the work necessary to form molecular-packing
defects.33 Therefore, this potential of defect formation can
manifest itself with a higher membrane permeability to water
and to small solutes.
Further, we base our reasoning for the compromised
stretching modulus observed for ATL1 on the to decrease in
the interfacial tension. We rule out the effect of membrane
thickness on stretching modulus, because both lipids show
similar thicknesses (Figure S2). We may follow Flory’s model,
in which the area compressibility modulus of a bilayer is derived
to be Ka = 6Π (where Π being the surface pressure of the
monolayer). In a flat, tension-free membrane, the surface
pressure of a monolayer is a constant of interfacial energy, γ for
the exposure of the hydrocarbon to water, thus Π = γ.
In conclusion, we used click-chemistry to develop a
hemicyclic tetraether scaffold incorporating phytanyl side
chains and 1,4 triazole rings. A new tetraether phospholipid
with 1,4 triazole rings in the hydrophobic core was readily
prepared and successfully used for small and giant vesicle
preparation suggesting that the new lipid scaffold offer great
flexibility for tailoring the functionality presented in the lipid
hydrophobic core, without compromising the ability to form
stable unilamellar vesicles. Whereas membranes made of the
new lipid displayed low retention for organic molecules in small
liposomes, water permeability in giant liposomes was found to
be similar to bilayer systems. We elucidated that the
incorporation of the relatively hydrophilic 1,4 triazole rings in
the hydrophobic core of an amphiphilic molecule could alter
the macroscopic properties of a membrane by increasing
DSC measurements; membrane thickness measurement;
calcein release assay; DIC images of GUVs; water
permeability data; elastic area compressibility modulus;
cohesive energy density; lysis tension; experimental
details; lipid synthesis; NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
ORCID
■
Author Contributions
⊥These authors contributed equally.
Funding
This work was supported by the Air Force Office of Scientific
Research (FA9550-12-1-0435) and the U.S. Army Research
Office (W911NF-15-1-0568).
Notes
The authors declare no competing financial interest.
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ASSOCIATED CONTENT
* Supporting Information
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S
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(11) Benvegnu, T.; Rethore, G.; Brard, M.; Richter, W.; Plusquellec,
The Supporting Information is available free of charge on the
D. Archaeosomes Based on Novel Synthetic Tetraether-Type Lipids
for the Development of Oral Delivery Systems. Chem. Commun. 2005,
44, 5536−5538.
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Chem. Mater. XXXX, XXX, XXX−XXX