1 research outputs found
Direct Measurement of the Effect of Cholesterol and 6‑Ketocholestanol on the Membrane Dipole Electric Field Using Vibrational Stark Effect Spectroscopy Coupled with Molecular Dynamics Simulations
Biological
membranes are heterogeneous structures with complex
electrostatic profiles arising from lipids, sterols, membrane proteins,
and water molecules. We investigated the effect of cholesterol and
its derivative 6-ketocholestanol (6-kc) on membrane electrostatics
by directly measuring the dipole electric field (<i>F</i>⃗<sub>d</sub>) within lipid bilayers containing cholesterol
or 6-kc at concentrations of 0–40 mol% through the vibrational
Stark effect (VSE). We found that adding low concentrations of cholesterol,
up to ∼10 mol %, increases <i>F</i>⃗<sub>d</sub>, while adding more cholesterol up to 40 mol% lowers <i>F</i>⃗<sub>d</sub>. In contrast, we measured a monotonic increase
in <i>F</i>⃗<sub>d</sub> as 6-kc concentration increased.
We propose that this membrane electric field is affected by multiple
factors: the polarity of the sterol molecules, the reorientation of
the phospholipid dipole due to sterol, and the impact of the sterol
on hydrogen bonding with surface water. We used molecular dynamics
simulations to examine the distribution of phospholipids, sterol,
and helix in bilayers containing these sterols. At low concentrations,
we observed clustering of sterols near the vibrational probe whereas
at high concentrations, we observed spatial correlation between the
positions of the sterol molecules. This work demonstrates how a one-atom
difference in a sterol changes the physicochemical and electric field
properties of the bilayer