Specific
Ion Interaction Dominates over Hydrophobic
Matching Effects in Peptide–Lipid Bilayer Interactions: The
Case of Short Peptide
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Abstract
Insertion of short peptides into
the cell membrane is energetically
unfavorable and challenges the commonly accepted hydrophobic matching
principle. Yet there has been evidence that many short peptides can
penetrate into the cells to perform the biological functions in salt
solution. On the basis of the previous study (J. Phys. Chem. C 2013, 117, 11095−11103), here we further performed a systematic study on the
interaction of mastoparan with various neutral lipid bilayers with
different lipid chain lengths in situ to examine the hydrophobic matching
principle in different aqueous salt environments using sum frequency
generation vibrational spectroscopy. It is found that the hydrophobic
matching is the dominant driving force for the association of MP with
a lipid bilayer in a pure water environment. However, in a kosmotropic
ion environment, the hydration of ions can overcome the hydrophobic
mismatching effects, leading to the insertion of MP into lipid bilayers
with much longer hydrophobic lengths. When the hydrophobic thickness
of the bilayer is much longer than MP’s hydrophobic length,
MP diffuses on a single monolayer, rather than spanning the bilayer
to prevent the exposure of the hydrophilic part of MP to the lipid
hydrophobic moiety. Findings from the present study suggest that the
interaction between the positively charged choline group of a lipid
and kosmotropic ions could be an important step for effective peptide
insertion into a cell membrane. Results from our studies will provide
an insight into how the short peptides form the ion channel in a thick
membrane and offer some ideas for cellular delivery