Biology subjects

Lanzani, G.

Publications and source records attributed to Lanzani, G..

6 recordsLinked to original sources

bioRxiv2026

A Dipolar Photoswitch Modulates Bacterial Membrane Potential and Reveals Context-dependent Bioelectrical Circuitry

Dynamic bioelectric signalling in bacteria regulates physiology and collective behaviours, yet tools to perturb microbial membrane voltage with high spatiotemporal control remain limited. Here we introduce MTP2, a non-genetic, membrane-targeting azobenzene photoswitch that enables optical modulation of bacterial membrane potential by tuning interfacial electrostatics in Bacillus subtilis. MTP2 associates strongly with the cell envelope and shifts the resting potential to more negative values in the dark, while 470-nm illumination evokes a robust, reversible depolarization at the single-cell level. Although MTP2 photoisomerization is ultrafast (picoseconds), the voltage waveforms unfold over seconds to minutes, indicating that the response is set by homeostatic ion transport rather than by MTP2 photochemistry. Genetic and pharmacological perturbations show that K+ conductance, Cl--sensitive pathways, and active transport reshape the amplitude, kinetics and even polarity of the optical response, revealing a context-dependent interplay between a passive molecular perturbation and endogenous bioelectric circuitry. As a functional proof of concept, kanamycin efficacy co-varies with the optically tuned voltage state. Together, these results establish MTP2 as a reversible chemical optostimulator for probing and controlling microbial electrophysiology.

microbiology↗

bioRxiv2024

A membrane-targeted photoswitch restores physiological ON/OFF responses to light in the degenerate retina

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch which modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in two distinct genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances. Intravitreally injected Ziapin2 in fully blind rd10 mice restored light-driven behavior and optomotor reflexes. The results indicate that Ziapin2 is a promising molecule for reinstating physiological visual responses in the late stages of retinal degeneration.

neuroscience↗

bioRxiv2022

Optical modulation of excitation-contraction coupling in human induced pluripotent stem cell-derived cardiomyocytes

Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field of research that aims to induce light sensitivity in living systems by exploiting exogeneous phototransducers. Here we propose a recently synthetized intramembrane photoswitch, based on an azobenzene derivative (Ziapin2), for optical pacing of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The light-mediated stimulation process has been studied by applying several characterization techniques to detect the effect on the cell properties. In particular, we recorded changes in membrane capacitance, in membrane potential (Vm), and modulation of intracellular Ca2+ dynamics. Finally, cell contractility was analyzed using a custom MATLAB algorithm. Photostimulation of intramembrane Ziapin2 causes a transient Vm hyperpolarization followed by a delayed depolarization and action potential firing. The observed initial electrical modulation nicely correlates with changes in Ca2+ dynamics and contraction rate. This work represents the proof of principle that Ziapin2 can modulate electrical activity and contractility in hiPSC-CMs, opening up a future development in cardiac physiology.

bioengineering↗

bioRxiv2022

P3HT-GRAPHENE DEVICE FOR THE RESTORATION OF VISUAL PROPERTIES IN A RAT MODEL OF RETINITIS PIGMENTOSA

Retinal degeneration is one of the prevalent causes of blindness worldwide, for which no effective treatment has yet been identified. Inorganic photovoltaic devices have been investigated for visual restoration in advanced stage Retinitis pigmentosa (RP), although lack of implant flexibility and foreign-object reactions have limited their application. Organic photoactive retinal prostheses may overcome these limitations, being biomimetic and tissue friendly. Inspired by organic photovoltaic strategies involving graphene, a hybrid retinal prosthesis was recently engineered consisting of a dual poly-3-hexylthiophene (P3HT) and graphene layer onto a flexible substrate. Here, this hybrid prosthesis was subretinally implanted in vivo in 5-month-old Royal College of Surgeons (RCS) rats, a rodent model of RP. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses. Moreover, the analysis of the physical-mechanical properties after prolonged permanence in the eye showed excellent biocompatibility and robustness of the device. Overall, the results demonstrate that graphene-enhanced organic photovoltaic devices can be suitably employed for the rescue of retinal dystrophies and supports the translation of the organic strategy into the medical practice. TABLE OF CONTENTSInspired by organic photovoltaic, a hybrid retinal prosthesis consisting of poly-3-hexylthiophene (P3HT) and graphene on a flexible substrate was subretinally implanted in vivo in Royal College of Surgeons (RCS) rats, a model of Retinitis pigmentosa. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=37 SRC="FIGDIR/small/507903v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1cb30a0org.highwire.dtl.DTLVardef@e57c2corg.highwire.dtl.DTLVardef@3b3c8corg.highwire.dtl.DTLVardef@10442d7_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Membrane Targeted Azobenzene Drives Optical Modulation of Bacterial Membrane Potential

Recent studies have shown that bacterial membrane potential is dynamic and plays signalling roles. Yet, little is still known about the mechanisms of bacterial membrane potential regulation -owing in part to a scarcity of appropriate research tools. Optical modulation of bacterial membrane potential could fill this gap and provide a new approach to studying and controlling bacterial physiology and electrical signalling. Here, we show that a membrane-targeted azobenzene (Ziapin2) can be used to photo-modulate the membrane potential in cells of the Gram-positive bacterium Bacillus subtilis. We found that upon exposure to blue-green light ({lambda} = 470 nm), isomerization of Ziapin2 in the bacteria membrane induces hyperpolarisation of the potential. In order to investigate the origin of this phenomenon we examined ion-channel-deletion strains and ion channel blockers. We found that in presence of the chloride channel blocker idanyloxyacetic acid-94 (IAA-94) or in absence of KtrAB potassium transporter, the hyperpolarisation response is attenuated. These results reveal that the Ziapin2 isomerization can induce ion channel opening in the bacterial membrane, and suggest that Ziapin2 can be used for studying and controlling bacterial electrical signalling. This new optical tool can contribute to better understand microbial phenomena, such as biofilm electric signalling and antimicrobial resistance.

biophysics↗

bioRxiv2019

A Membrane-Targeted Photoswitch Potently Modulates Neuronal Firing

Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. We engineered novel light-sensitive molecules by adding polar groups to a hydrophobic backbone containing azobenzene and azepane moieties. We demonstrate that the probes stably partition into the plasma membrane, with affinity for lipid rafts, and cause thinning of the bilayer through their trans-dimerization in the dark. In neurons pulse-labeled with the compound, light induces a transient hyperpolarization followed by a delayed depolarization that triggers action potential firing. The fast hyperpolarization is attributable to a light-dependent decrease in capacitance due to membrane relaxation that follows disruption of the azobenzene dimers. The physiological effects are persistent and can be evoked in vivo after labeling the mouse somatosensory cortex. These data demonstrate the possibility to trigger neural activity in vitro and in vivo by modulating membrane capacitance, without directly affecting ion channels or local temperature.

neuroscience↗