Complex Behavior of Phosphatidylcholine–Phosphatidic Acid Bilayers and Monolayers: Effect of Acyl Chain Unsaturation

Phosphatidic
acids (PAs) have many biological functions in biomembranes,
e.g., they are involved in the proliferation, differentiation, and
transformation of cells. Despite decades of research, the molecular
understanding of how PAs affect the properties of biomembranes remains
elusive. In this study, we explored the properties of lipid bilayers
and monolayers composed of PAs and phosphatidylcholines (PCs) with
various acyl chains. For this purpose, the Langmuir monolayer technique
and atomistic molecular dynamics (MD) simulations were used to study
the miscibility of PA and PC lipids and the molecular organization
of mixed bilayers. The monolayer experiments demonstrated that the
miscibility of membrane components strongly depends on the structure
of the hydrocarbon chains and thus on the overall lipid shape. Interactions
between PA and PC molecules vary from repulsive, for systems containing
lipids with saturated and unsaturated acyl tails (strongly positive
values of the excess free energy of mixing), to attractive, for systems
in which all lipid tails are saturated (negative values of the excess
free energy of mixing). The MD simulations provided atomistic insight
into polar interactions (formation of hydrogen bonds and charge pairs)
in PC–PA systems. H-bonding between PA monoanions and PCs in
mixed bilayers is infrequent, and the lipid molecules interact mainly
via electrostatic interactions. However, the number of charge pairs
significantly decreases with the number of unsaturated lipid chains
in the PA–PC system. The PA dianions weakly interact with the
zwitterionic lipids, but their headgroups are more hydrated as compared
to the monoanionic form. The acyl chains in all PC–PA bilayers
are more ordered compared to single-component PC systems. In addition,
depending on the combination of lipids, we observed a deeper location
of the PA phosphate groups compared to the PC phosphate groups, which
can alter the presentation of PAs for the peripheral membrane proteins,
affecting their accessibility for binding.