The Effect of an Intramembrane Light-Actuator on the Dynamics of Phospholipids in Model Membranes and Intact Cells

The noncovalent intercalation of amphiphilic molecules in the lipid membrane can be exploited to modulate efficiently the physical status of the membrane. Such effects are largely employed in a range of applications, spanning from drug-delivery to therapeutics. In this context, we have very recently developed an intramembrane photo-actuator consisting of an amphiphilic azobenzene molecule, namely ZIAPIN2. The selective photo-isomerization occurring in the lipid bilayer induces a photo-triggered change in the membrane thickness and capacitance, eventually permitting to evoke light-induced neuronal firing both in vitro and in vivo. Here, we present a study on the dynamical perturbation in the lipid membrane caused by ZIAPIN2 and its vehicle solvent, dimethyl sulfoxide. Effects on the dynamics occurring in the picosecond time range and at the molecular level are probed using quasi-elastic neutron scattering. By coupling experiments carried out both on model membranes and intact cells, we found that DMSO leads to a general retardation of the dynamics within a more dynamically ordered landscape, a result that we attribute to the dehydration at the interface. On the other hand, ZIAPIN2 partitioning produces a general softening of the bilayer owing to its interaction with the lipids. These data are in agreement with our recent studies, which indicate that the efficacy of ZIAPIN2 in triggering cellular signalling stems from its ability to mechanically perturb the bilayer as a whole, by forming light-sensitive membrane spanning dimers.