# Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

## TL;DR

A photoswitchable rotaxane can control membrane permeability in lipid vesicles, with effects varying based on lipid composition and light exposure.

## Contribution

The study reveals how lipid composition and rotaxane structure influence light-triggered membrane permeabilization.

## Key findings

- Photoswitching increased dye release in EYPC/Chol 8:2 vesicles from 29% to 59%.
- Azobenzene photoswitching had minimal effect on rigid EYPC/Chol 6:4 bilayers.
- An unknown irreversible process triggered dye release in EYPC vesicles when the unthreaded axle was irradiated.

## Abstract

This study investigated a rotaxane featuring azobenzene photoswitches in its macrocycle and its ability to modulate membrane permeability in large unilamellar vesicles (LUVs) of varying lipid compositions. Upon photoisomerization, the rotaxane significantly enhanced the release of the hydrophilic dye sulforhodamine B in vesicles composed of EYPC/Chol 8:2, with release increasing from 29% (non-irradiated) to 59% (irradiated). Moreover, gel-phase DPPC bilayers also exhibited an increase in release from 7% to 14%. On the contrary, highly fluid pure EYPC bilayers showed high baseline release upon rotaxane incorporation (64%), with photoswitching producing only a slight increase (70%), as most dye was released within the first minutes of rotaxane insertion. Likewise, azobenzene photoswitching did not induce permeabilization in the more rigid and thicker EYPC/Chol 6:4 bilayers, which showed minimal release (5%). Furthermore, we discovered that when the unthreaded axle is irradiated with light, an unknown, irreversible photochemical process occurs, which triggers the release from only the vesicles containing EYPC. These findings underscore the significance of both the physical and chemical properties of the bilayer in enabling effective light-triggered cargo release through rotaxane activation.