image: Figure | Working principle of the intelligent metasurface. a, an illustrative scenario for monitoring peoples in a typical indoor environment in a smart, real-time and inexpensive way, where the intelligent metasurface decorated as a part of wall is used to adaptively manipulate ambient Wi-Fi signals. b, The schematic configuration of intelligent metasurface system by coming a large-aperture programmable metasurface for manipulating and sampling the EM wavefields adaptively with artificial neural networks (ANNs) for controlling and processing the data flow instantly. The intelligent metasurface has two operational modes: active and passive modes. In the active mode, the intelligent system has a transmitting antenna and a receiving antenna. In the passive mode, the intelligent system has a pair of receiving antennas. (c), Microwave data processing flow by using deep learning CNNs. In (c), the microwave data are processed with IM-CNN-1to form the image of the whole human body. Then, the Faster R-CNN is performed to find the region of interest (ROI) from the whole image, for instance, the chest for respiration monitoring, and the hand for sign language recognition. Afterwards, the G-S algorithm is used to find the coding sequence for controlling the programmable metasurface such that its associated radiation beams can be focused toward the desirable spot. IM-CNN-2 processes microwave data to recognize the hand sign; and the human breathing is identified by the time-frequency analysis of microwave data.
Credit: Valentina Sesti, Arianna Magni et al.
Direct electrical stimulation of cells is a valid therapy for treating neuronal disorders that do not respond to pharmacological treatment, but it also has drawbacks due to the use of metal electrodes. The use of light for cell stimulation is less invasive, has limited collateral effects, and high spatial and temporal resolution. However, it requires a system to transduce photons into a biological stimulus. Existing solutions suffer from limited lifetime, may perturb the cell state even in dark, or require the use of viral vectors.
In a new paper published in Light: Science & Application, a multi-disciplinary team of scientists, that include Chemist, Physicists, Biotechnologist and Neuroscientist have developed new tools for cell stimulation, namely intramembrane azobenzenes with a push-pull character.
These molecules are water soluble and pioneer a different photostimulation paradigm, that is the light-induced modulation of the plasma membrane surface charge. A series of new ABs was synthesized, having in common the electron acceptor group NO2, and varying numbers of alkyl chains capped with cationic groups. The latter serves a dual role as membrane anchors and electron-donor groups. All molecules have been designed to exhibit an amphiphilic character able to interact with the lipid bilayer, not unlike the reported photoswitchable lipids38. After the experimental screening of all molecules in the series, based on their ability to partition into the membrane and induce light-dependent membrane potential changes, the team selected the best candidate for physiological applications, namely MTP. Through optical spectroscopy, they assessed the push-pull character of this molecule and its ability to undergo isomerisation in the biological setting. The photophysical study shows that following photoexcitation MTP isomerizes in about 10 ps, with a slightly larger yield and a 6-fold longer lifetime of the cis isomer in SDS (300 s) compared to water. Molecular dynamics simulation supports the conjecture of intra membrane portioning and provides hints on the distribution in space.
Light absorption by push-pull azobenzenes dwelling in the membrane causes a change in the surface charge triggered by the molecular dipole electric field. This variation is associated with a displacement of charges due to a movement of ions across the membrane, coherent with experimentally measured inward currents. Authors claim that “MTP2 emerges as a non-genetic optostimulation tool, capitalizing on the precise modulation of relevant electric characteristics of the lipid membrane.”
The research team believe that “This phenomenon enlarges the range of the existing cell opto-stimulation mechanisms, traditionally based on opto-capacitance, electrostatic coupling, ion channel gating or membrane poration.”
In addition, they note that: “Our molecules exhibit high water solubility, higher trans-cis interconversion rate and, crucially, they remain inactive in the dark state.”
The paper reports light-evoked membrane potential modulation driven by MTP in cell lines, primary neurons and hiPSC-CMs.
Finally, authors comment on the possible application. The rapid light-induced depolarization, although insufficient to trigger an action potential, holds potentiality for other advanced applications. Specifically, sub-threshold optical stimulation could be used to destabilize and terminate re-entry-based arrhythmias (e.g., spiral waves).
Article Title
Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential