Mesoscopic models of lipid bilayers and bilayers with embedded ...

agreement we find gives us confidence in the ability of our coarse-grained approach
to model real phospholipids systems.
Lateral pressure in lipid bilayers
While the surface tension of a lipid bilayer, or monolayer, can be measured experimentally,
there are no experimental techniques to measure the local distribution of
pressure. Simulations can then be an helpful tool to characterize the shape of the
pressure profile in lipid bilayers. The study of the effect of local redistribution of
lateral pressure in bilayers induced by site dependent changes in the lipid topology
can help to answer some important questions. Can shifts in the lateral pressure be
induced by changes in the lipid structure, like different level of unsaturation in the
chain? How do these changes depend on the position and nature of the modification
in the lipid topology? A related and interesting question is the possible correlation
between the local distribution of the pressure profile and the partitioning of small
molecules in the bilayer: where do small solutes preferentially adsorb in a lipid bilayer?
And, is the partitioning of solutes correlated to the distribution of pressure
within the bilayer? To address these questions, in Chapter 4 we describe the shape
of the lateral pressure distribution in lipid bilayers for different lipid topologies. We
show that the pressure distribution is tightly correlated with the density distribution,
i.e. with the localization of the lipid segments within the bilayer, while it is less sensitive
to the functional form and parameterization of the interaction potentials. To
support the latter observation, we compare the pressure profile in a bilayer of coarsegrained
double-tail lipids with the pressure profile computed in atomistic molecular
dynamics simulations of a DPPC bilayer. We show that the shapes of the pressure
profiles calculated with the two different approaches have remarkable similarities.
In Chapter 6 we investigate the interaction of small solutes, which can model
anesthetics, with the lipid bilayers. We show that the partitioning of small solutes
molecules in a bilayer is mainly driven by chemical affinity, i.e. by the degree of hydrophobicity
of the solutes. But also another effect is found; these molecules locate
preferentially in the region of the bilayer where the pressure profile has local minima.
These observations can help to predict the partitioning of molecules like anesthetics
in the bilayer. Furthermore, we show that, if the molecules are located in
the headgroups region of the bilayer, they significantly decrease the local pressure in
this region. Since anesthetics are also incorporated in the bilayer interfacial region,
we postulate that these molecules could regulate the activity of membrane proteins
trough changes is the pressure distribution.
The hydrophobic mismatch
In Chapter 7 we extend the coarse-grained model, and apply it to the study of lipid
bilayers with embedded proteins, at low protein-to-lipid ratios. In particular we in-
127