INVESTIGADORES
PASTORINO Claudio
artículos
Título:
Comparison of Ternary Bilayer Mixtures with Asymmetric or Symmetric Unsaturated Phosphatidylcholine Lipids by Coarse Grained Molecular Dynamics Simulations
Autor/es:
PASTORINO, C.; ROSETTI C. M.
Revista:
JOURNAL OF PHYSICAL CHEMISTRY B - (Print)
Editorial:
AMER CHEMICAL SOC
Referencias:
Lugar: Washington; Año: 2012 vol. 116 p. 3525 - 3537
ISSN:
1520-6106
Resumen:
We studied the phase behavior of various ternary bilayer mixtures
composed of cholesterol, an unsaturated lipid, and a fully saturated
lipid, by means of molecular dynamics simulations of the MARTINI(1)
coarse grain model. We aimed at comparing lateral organization and
local properties of bilayers containing phosphatidylcholine (PC) lipids,
either with two unsaturated tails (symmetric), or one unsaturated and
one saturated tail (asymmetric), as the low-melting component of the
mixture. The number of unsaturations per chain was systematically varied
in both classes of unsaturated lipids, to account for its consequences
in segregation. In the asymmetric unsaturated PCs, the saturated tail
was kept identical to the hydrophobic chains of the fully saturated
lipid component. Membranes with a symmetric or an asymmetric unsaturated
lipid, with the same kind of unsaturated chain, show different phase
behavior. Symmetric polyunsaturated PCs set the separation in two
phases. Instead, the asymmetric polyunsaturated lipids induced nonideal
mixing of components in single-phase bilayers. A significative drop of
temperature, within the accessible temperature range, enhances the
segregation in mixtures with the more unsaturated asymmetric PC, but
still within a single phase. This different phase behavior between
membranes with symmetric and asymmetric unsaturated PCs is also observed
for lipids with the same total number of unsaturations. On the other
hand, the degree of unsaturation per se enhances the segregation, by
increasing the composition fluctuations in single-phase membranes with
asymmetric PC lipids, and raising the line tension in the two-phase
bilayer mixtures with symmetric polyunsaturated PCs. Dynamic clusters of
unsaturated asymmetric lipids can be identified. The clusters show no
correlation between leaflets, as observed for the phase domains in
mixtures with the symmetric polyunsaturated PCs. Interestingly, we found
that asymmetric PC lipids have a preferential orientation such that
their saturated tails increase their density toward the periphery of the
clusters, facing regions enriched in the fully saturated lipids and
cholesterol. The degree of unsaturation increases the cluster size and
also enhances the anisotropy of the orientation. The surface density of
cholesterol follows a gradient that favors its interaction with the
saturated tails. Such gradients in composition lead to gradients in
order parameters, such as the conformational order and the area of the
tails, which increases away from the unsaturated lipid clusters. We
compared, in addition, differences in hydrophobic length mismatch
between acyl chains of the low-melting and high-melting components, in
mixtures containing either symmetric or asymmetric unsaturated lipids.