Computational Characterization of a Cholesterol-Based Molecular Rotor in Lipid Membranes

Biophysical
properties of cellular membranes critically depend
on their content of cholesterol and its interaction with various other
lipid species. Cholesterol-dependent friction at the nanoscale can
be studied with molecular rotors, whose quantum yield depends on rotational
dynamics of functional groups during their excited state lifetime.
Here, we present a detailed computational analysis of a phenyl–BODIPY-linked
cholesterol based molecular rotor in direct comparison with the well-known
TopFluor-cholesterol. We describe a new parametrization strategy of
force field parameters for the BODIPY moiety and carry out extensive
molecular dynamics simulations of the probe in membranes in the absence
or presence of cholesterol. Our study quantifies the extent of membrane
perturbation by these probes, analyzes their tilting resistance in
the bilayer and derives dynamic properties directly related to the
rotor propensity. We show that phenyl–BODIPY-cholesterol bears
potential as a cholesterol-dependent molecular rotor to report about
microviscosity of sterol-containing model and cell membranes.