Membrane Environment Enables Ultrafast Isomerization of Amphiphilic Azobenzene

Abstract

The non‐covalent affinity of photoresponsive molecules to biotargets represents an attractive tool for achieving effective cell photo‐stimulation. Here, an amphiphilic azobenzene that preferentially dwells within the plasma membrane is studied. In particular, its isomerization dynamics in different media is investigated. It is found that in molecular aggregates formed in water, the isomerization reaction is hindered, while radiative deactivation is favored. However, once protected by a lipid shell, the photochromic molecule reacquires its ultrafast photoisomerization capacity. This behavior is explained considering collective excited states that may form in aggregates, locking the conformational dynamics and redistributing the oscillator strength. By applying the pump probe technique in different media, an isomerization time in the order of 10 ps is identified and the deactivation in the aggregate in water is also characterized. Finally, it is demonstrated that the reversible modulation of membrane potential of HEK293 cells via illumination with visible light can be indeed related to the recovered trans→cis photoreaction in lipid membrane. These data fully account for the recently reported experiments in neurons, showing that the amphiphilic azobenzenes, once partitioned in the cell membrane, are effective light actuators for the modification of the electrical state of the membrane.

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

“…In regards of ZIAPIN2 and DMSO localization in HEK293 cells, in our previous studies 23,24 we found that more than 70% of Ziapin2 was localized to the neuronal surface, with a coverage of ~15% of the total membrane surface that progressively decreased over time (t 1/2 = 36.4 h, confocal microscopy data). The occurrence of fluorescence resonance energy transfer between ZIAPIN2 and the membrane dye CellMask further demonstrates that the molecule is strictly localized to the membrane bilayer.…”

“…Full details about the synthesis can be found in our previous papers. 23,24 Liposome preparation. 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was purchased from Avanti Polar Lipids and used without further purification.…”

“…[18][19][20][21][22] We have recently developed an amphiphilic azobenzene molecule named ZIAPIN2, which partitions stably into the plasma membrane where it can work selectively as an efficient optomechanical actuator. 23,24 In particular, while the dark-adapted trans isomer causes a thinning of the lipid bilayer via a dimerization mechanism, illumination with visible light leads to a membrane relaxation that follows disruption of the azobenzene dimers. This, in turn, enables the cell membrane capacitance to be modulated and, remarkably permits to evoke light-induced neuronal firing in vitro as well in vivo.…”

Optical Isomerization and Photo-Patternable Properties of GeO2/Ormosils Organic-Inorganic Composite Films Doped with Azobenzene

“…Under visible light or heated conditions, cis isomers are transformed into trans isomers [9]. Therefore, the photoisomerization of azobenzene makes it a promising optical switch in the fields of chemical engineering, biomedicine and optoelectronics [10][11][12]. Photoisomerization based on azobenzene also makes polymers containing azobenzene molecules have photo-isomerization characteristics.…”

A Polymer Blend Substrate for Skeletal Muscle Cells Alignment and Photostimulation

“…Phototransducers may come in a variety of shapes and structures, such as plasmonic nanodots, [ 6,7 ] inorganic semiconductors devices, [ 8–10 ] nanostructures, [ 11–14 ] organic semiconductors [ 15–19 ] and small molecules. [ 20,21 ] Thanks to the similarity in composition and structure with biomolecules, organic semiconductors and molecular compounds express higher biocompatibility and multifunctional actuation. Their peculiar photophysical properties allow the employment of different photostimulation mechanisms (i.e., electrical, mechanical or thermal) and at the same time, their mechanical flexibility favors conformational matching that is crucial for in vivo applications.…”