Multimillion Atom
Simulations of Di-8-ANEPPS Chromophores
Embedded in a Model Plasma Membrane: Toward the Investigation of Realistic
Dyed Cell Membranes
posted on 2023-12-29, 16:33authored byCharlotte Bouquiaux, Benoît Champagne, Pierre Beaujean
A multistep computational approach has been employed
to study a
multimillion all-atom dyed plasma membrane, with no less than 42 different
lipid species spanning the major head groups and a variety of fatty
acids, as well as cholesterol, with the objective of investigating
its structure and dynamics, as well as its impact on the embedded
di-8-ANEPPS dyes. The latter are commonly used as bioimaging probes
and serve as local microscopes. So, they provide information on membrane
morphology via their second harmonic nonlinear optical (NLO) responses,
which have the advantage of being specific to interface regions and
sensitive to the chromophore environment. In previous studies, this
chromophore has only been studied in simpler membrane models, far
from the complexity of real lipid bilayers, while, owing to the ever-increasing
computational resources, multimillion lipid bilayers have been studied,
giving access to the effects of its heterogeneity. First, using molecular
dynamics (MD) simulations, it is found that the combination of lipids
produces a more ordered and denser membrane compared to its homogeneous
model counterparts, while the local environment of the embedded dyes
becomes enriched in phosphatidylcholine. Subsequently, the second
harmonic first hyperpolarizability of the probes was calculated at
the TDDFT level on selected frames of MD, highlighting the influence
of the lipid environment. Due to the complexity of the system, machine
learning (ML) tools have been employed to establish relationships
between the membrane structural parameters, the orientation of the
probes, and their NLO responses. These ML approaches have revealed
influential features, including the presence of diacylglycerol lipids
close to the dye. On the whole, this work provides a first step toward
understanding the cooperation, synergy, and interactions that occur
in such complex guest–host environments, which have emerged
as new targets for drug design and membrane lipid therapy.