Interfacial Glucose to Regulate Hydrated Lipid Bilayer Properties: Influence of Concentrations

A series of atomistic molecular dynamics (MD) simulations
were
carried out with a hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine
(DMPC) bilayer with the variation of glucose concentrations from 0
to 30 wt % in the presence of 0.3 M NaCl. The study suggested that
although the thickness of the lipid bilayer dropped significantly
with the increase in glucose concentration, it expanded laterally
at high glucose levels due to the intercalation of glucose between
the headgroups of adjacent lipids. We adopted the surface assessment
via the grid evaluation method to compute the deviation of the bilayer’s
key structural features for the different amounts of glucose present.
This suggested that the accumulation of glucose molecules near the
headgroups influences the local lipid bilayer undulation and crimping
of the lipid tails. We find that the area compressibility modulus
increases with the glucose level, causing enhanced bilayer rigidity
arising from the slow lateral diffusion of lipids. The restricted
lipid motion at high glucose concentrations controls the sustainability
of the curved bilayer surface. Calculations revealed that certain
orientations of CO⃗ of interfacial glucose with the PN⃗ of lipid headgroups are preferred, which
helps the glucose to form direct hydrogen bonds (HBs) with the lipid
headgroups. Such lipid–glucose (LG) HBs relax slowly at low
glucose concentrations and exhibit a higher lifetime, whereas fast
structural relaxation of LG HBs with a shorter lifetime was noticed
at a higher glucose level. In contrast, lipid–water (LW) HBs
exhibited a higher lifetime at a higher glucose level, which gradually
decreased with the glucose level lowering. The study interprets that
the glucose concentration-driven LW and LG interactions are mutually
inclusive. Our detailed analysis will exemplify small saccharide concentration-driven
membrane stabilizing efficiency, which is, in general, helpful for
drug delivery study.