Abstract

Oxidation of cellular structures is typically an undesirable process that can be a hallmark of certain diseases. On the other hand, photooxidation is a necessary step of photodynamic therapy (PDT), a cancer treatment causing cell death upon light irradiation. Here, the effect of photooxidation on the microscopic viscosity of model lipid bilayers constructed of 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine has been studied. A molecular rotor has been employed that displays a viscosity‐dependent fluorescence lifetime as a quantitative probe of the bilayer's viscosity. Thus, spatially‐resolved viscosity maps of lipid photooxidation in giant unilamellar vesicles (GUVs) were obtained, testing the effect of the positioning of the oxidant relative to the rotor in the bilayer. It was found that PDT has a strong impact on viscoelastic properties of lipid bilayers, which ‘travels’ through the bilayer to areas that have not been irradiated directly. A dramatic difference in viscoelastic properties of oxidized GUVs by Type I (electron transfer) and Type II (singlet oxygen‐based) photosensitisers was also detected.

Highlights

  • Unsaturated lipids are commonly found in the variety of biological membranes and are vulnerable to reactive oxygen species (ROS) such as singlet oxygen and oxygen-based radicals

  • Even though porphyrin dimer (PD) absorbs at 480 nm, its fluorescence is centred at 630-750 nm,[39] which does not overlap with fluorescence of BODIPY-C10 (510-600 nm)

  • We have utilised a hydrophobic molecular rotor that was fully embedded in a lipid bilayer to probe the effect of photooxidation on the bilayer viscosity

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Summary

Introduction

Unsaturated lipids are commonly found in the variety of biological membranes and are vulnerable to reactive oxygen species (ROS) such as singlet oxygen and oxygen-based radicals. Extreme oxidation of cellular components can lead to cell death via apoptosis or necrosis, and this effect is successfully used in photodynamic therapy (PDT), a modality of cancer treatment.[4] PDT is a light activated process where a ‘photosensitizer’, a molecule that produces ROS upon excitation by an appropriate wavelength of light, is targeted to malignant cells and tissues. Produced ROS efficiently oxidise cellular components leading to the death of targeted cells. Given their abundance in cells, lipids serve as primary targets for ROS during PDT and membrane oxidation is a key step leading to cell apoptosis.[5,6]

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