Xanthophylls (polar carotenoids) play diverse biological roles, among which are modulation of the physical properties of lipid membranes and protection of biomembranes against oxidative damage. Molecular mechanisms underlying these functions are intimately related to the localization and orientation of xanthophyll molecules in lipid membranes. In the present work, we address the problem of localization and orientation of two xanthophylls present in the photosynthetic apparatus of plants and in the retina of the human eye, zeaxanthin and lutein, in a single lipid bilayer membrane formed with dimyristoylphosphatidylcholine. By using fluorescence microscopic analysis and Raman imaging of giant unilamellar vesicles, as well as molecular dynamics simulations, we show that lutein and zeaxanthin adopt a very similar transmembrane orientation within a lipid membrane. In experimental and computational approach, the average tilt angle of xanthophylls relative to the membrane normal is independently found to be ~40 deg, and results from hydrophobic mismatch between the membrane thickness and the distance between the terminal hydroxyl groups of the xanthophylls. Consequences of such a localization and orientation for biological activity of xanthophylls are discussed.
Amphotericin B is a popular antifungal antibiotic, a gold standard in treatment of systemic mycotic infections, due to its high effectiveness. On the other hand, applicability of the drug is limited by its considerable toxicity to patients. Biomembranes are a primary target of physiological activity of amphotericin B and both the pharmacologically desired and toxic side effects of the drug relay on its molecular organization in the lipid phase. In the present work, molecular organization, localization and orientation of amphotericin B, in a single lipid bilayer system, was analysed simultaneously, thanks to application of a confocal fluorescence lifetime imaging microscopy of giant unilamellar vesicles. The results show that the presence of sterols, in the lipid phase, promotes formation of supramolecular structures of amphotericin B and their penetration into the membrane hydrophobic core. The fact that such an effect is substantially less pronounced in the case of
cholesterol than ergosterol, the sterol of fungal membranes, provides molecular insight into the selectivity of the drug.
The functioning of
the human eye in the extreme range of light
intensity requires a combination of the high sensitivity of photoreceptors
with their photostability. Here, we identify a regulatory mechanism
based on dynamic modulation of light absorption by xanthophylls in
the retina, realized by reorientation of pigment molecules induced
by
trans
–
cis
photoisomerization.
We explore this photochemically switchable system using chromatographic
analysis coupled with microimaging based on fluorescence lifetime
and Raman scattering, showing it at work in both isolated human retina
and model lipid membranes. The molecular mechanism underlying xanthophyll
reorientation is explained in terms of hydrophobic mismatch using
molecular dynamics simulations. Overall, we show that xanthophylls
in the human retina act as “molecular blinds”, opening
and closing on a submillisecond timescale to dynamically control the
intensity of light reaching the photoreceptors, thus enabling vision
at a very low light intensity and protecting the retina from photodegradation
when suddenly exposed to strong light.
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