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

Abstract

The non-covalent 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.

A Comparative Study on DMSO-Induced Modulation of the Structural and Dynamical Properties of Model Bilayer Membranes

“…Baiz and his co-workers have recently employed two-dimensional infrared spectroscopy (2D IR) and molecular dynamics simulations to investigate the effects of DMSO on hydrogen bond dynamics at the lipid–water interface. In this regard, the quasi-elastic neutron scattering (QENS) technique is significantly advantageous over other complementary techniques because it is used to study the effect of different additives on the phase behavior and dynamics of the lipid bilayers. , It provides spatial information about the dynamical motions of the bilayers in the form of wave vector transfer, Q , dependence with time scales of ∼10 –13 –10 –9 s and at length scales from angstroms to nanometers. , The QENS technique probes a broad range of time and length scales, including (1) lateral slower diffusion of lipid molecules and (2) a relatively faster localized internal motion of the lipid molecules . In this technique, the dynamics of lipid molecules can predict the lipid bilayer properties that in turn dictate the transport properties of the membrane .…”

“…38,39 The QENS technique probes a broad range of time and length scales, including (1) lateral slower diffusion of lipid molecules and (2) a relatively faster localized internal motion of the lipid molecules. 40 In this technique, the dynamics of lipid molecules can predict the lipid bilayer properties that in turn dictate the transport properties of the membrane. 41 However, direct evidence showing how the bilayer fluidity affects the water dynamics in the interior and vicinity of the lipid membranes in the presence of DMSO is still being sought.…”

Membrane Targeted Azobenzene Drives Optical Modulation of Bacterial Membrane Potential

“…Partitioning of Ziapin2 into the bacterial membrane was further supported by UV-Vis and photoluminescence spectroscopies, as it happens for eukaryotic cells [10,26] . Specifically, the absorption spectrum of Ziapin2 in bacteria displays a better resolved vibronic progression and a broader linewidth in comparison to Ziapin2 in phosphate buffer saline (PBS) (Figure 2c), an effect that has been attributed to H-aggregation of the chromophore inside the lipid membrane and can be linked to Ziapin2 dimerization at this location.…”

Shedding Light on Thermally Induced Optocapacitance at the Organic Biointerface

“…The cell membrane is the natural target for this approach. 2 − 5 In particular, membrane potential modulation occurs via the photoinduced modification of the cell membrane electrical properties, such as resistance, capacitance, and resting potential, 2 either through direct photostimulation 6 or using selected transducers that are able to convert light into an electrical, mechanical, chemical, or thermal stimulus. 7 − 11 In the last decade, organic semiconductors have emerged as powerful photoactuators for the development of functional interfaces with living cells and organisms.…”

“…Optical technologies are particularly suited for this purpose, as light enables precise and localized perturbation of cell activity in a remote and spatiotemporal precise manner. The cell membrane is the natural target for this approach. − In particular, membrane potential modulation occurs via the photoinduced modification of the cell membrane electrical properties, such as resistance, capacitance, and resting potential, either through direct photostimulation or using selected transducers that are able to convert light into an electrical, mechanical, chemical, or thermal stimulus. − In the last decade, organic semiconductors have emerged as powerful photoactuators for the development of functional interfaces with living cells and organisms. These systems, which have benefited from a long period of development and refinement for applications in organic photovoltaics, exhibit a relatively high absorption coefficient (α ∼ 10 5 cm –1 ) in the visible spectral range, which is suitable for light biostimulation.…”