ct400431e_si_001.pdf (739.57 kB)
Simulation Study of the Structure and Phase Behavior of Ceramide Bilayers and the Role of Lipid Headgroup Chemistry
journal contribution
posted on 2013-11-12, 00:00 authored by Shan Guo, Timothy
C. Moore, Christopher R. Iacovella, L. Anderson Strickland, Clare McCabeCeramides are known to be a key component
of the stratum corneum,
the outermost protective layer of the skin that controls barrier function.
In this work, molecular dynamics simulations are used to examine the
behavior of ceramide bilayers, focusing on nonhydroxy sphingosine
(NS) and nonhydroxy phytosphingosine (NP) ceramides. Here, we propose
a modified version of the CHARMM force field for ceramide simulation,
which is directly compared to the more commonly used GROMOS-based
force field of Berger (Biophys. J. 1997, 72, 2002–2013); while both force fields
are shown to closely match experiment from a structural standpoint
at the physiological temperature of skin, the modified CHARMM force
field is better able to capture the thermotropic phase transitions
observed in experiment. The role of ceramide chemistry and its impact
on structural ordering is examined by comparing ceramide NS to NP,
using the validated CHARMM-based force field. These simulations demonstrate
that changing from ceramide NS to NP results in changes to the orientation
of the OH groups in the lipid headgroups. The arrangement of OH groups
perpendicular to the bilayer normal for ceramide NP, versus parallel
for NS, results in the formation of a distinct hydrogen bonding network,
which is ultimately responsible for shifting the gel-to-liquid phase
transition to higher temperature, in direct agreement with experiment.