engleski

Cholesterol under oxidative stress - how lipid membranes sense oxidation as cholesterol is being replaced by oxysterols

The behavior of oxysterols in phospholipid membranes and their effects on membrane properties was investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and molecular modeling. Two families of oxysterols were scrutinized – tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similarly to cholesterol in terms of molecular orientation roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They can acquire tilted orientations and, therefore, more strongly disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membrane.

phospholipid bilayers; oxysterols; molecular dynamics simulations; DPH anisotropy; NMR measurements; Laurdan fluorescence; liposomes; tilt modulus

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