Photodynamic therapy with Photoditazine increases microviscosity of cancer cells membrane in cellulo and in vivo.

Photodynamic therapy (PDT) is a minimally invasive method for cancer treatment, one of the effects of which is the oxidation of membrane lipids. However, changes in biophysical properties of lipid membranes during PDT have been poorly explored. In this work, we investigated the effects of PDT on membrane microviscosity in cancer cells in the culture and tumor xenografts. Membrane microviscosity was visualized using fluorescence lifetime imaging microscopy (FLIM) with a viscosity-sensitive rotor BODIPY2. It was found that PDT using chlorine e6-based photosensitizer Photoditazine caused a quick, steady elevation of membrane microviscosity both in cellulo and in vivo. The proposed mechanisms responsible for the increase in microviscosity was lipid peroxidation by reactive oxygen species that resulted in a decrease of phosphatidylcholine and the fraction of unsaturated fatty acids in the membranes. Our results suggest that the increased microviscosity is an important factor that contributes to tumor cell damage during PDT.

Transition State Stabilizing Effects of Oxygen and Sulfur Chalcogen Bond Interactions.

Non-covalent chalcogen bond (ChB) interactions have found utility in many fields, including catalysis, organic semiconductors, and crystal engineering. In this study, the kinetic effects of ChB interactions of oxygen and sulfur were experimentally measured using a series of molecular rotors. The rotors were designed to form ChB interactions in the bond rotation transition states. This enabled their kinetic influences to be assessed by monitoring changes in rotational barriers. Despite forming weaker ChB interactions, the smaller chalcogens were able to stabilize transition states and had measurable kinetic effects. Sulfur stabilized the bond rotation transition state by as much as -7.2 kcal/mol without electron-withdrawing groups. The key was to design a system where the sulfur ðœŽ-hole was aligned with the lone pairs of the chalcogen bond acceptor. Oxygen rotors also could form transition state stabilizing ChB interactions but required electron-withdrawing groups. For both oxygen and sulfur ChB interactions, a strong correlation was observed between transition state stabilizing abilities and electrostatic potential (ESP) of the chalcogen, providing a useful predictive parameter for the rational design of future ChB systems.

Spatially Confined Assembly and Immobilization of Hierarchical Nanoparticle Architectures inside Microdroplets in Magnetic Fields.

Magnetic field-directed colloidal interactions offer facile tools for assembly of structures that range from linear chains to multidimensional hierarchical architectures. While the field-driven assembly of colloidal particles has commonly been investigated in unbounded media, a knowledge gap remains concerning such assembly in confined microenvironments. Here, we investigate how confinement of ferromagnetic nanoparticles in microspheres directs their magnetic assembly into hierarchical architectures. Microdroplets from polydimethylsiloxane (PDMS) liquid precursor containing dispersed iron oxide magnetic nanoparticles (MNPs) were placed in a static magnetic field leading to the formation of organized assemblies inside the host droplets. By changing the MNP concentrations, we revealed a sequence of microstructures inside the droplets, ranging from linear chains at a low MNP loading, transitioning to a combination of chains and networked bundles, to solely 3D bundles at high MNP loading. These experimental results were analyzed with the aid of COMSOL simulations where we calculated the potential energy to identify the preferred assembly conformations. The chains at high MNP loading minimized their energy by aggregating laterally to form bundles with their MNP dipoles being out-of-registry. We cured these PDMS droplets to immobilize the assemblies by forming soft microbeads. These microbeads constitute an "interaction toolbox" with different magnetic macroscale responses, which are governed by the structuring of the MNPs and their magnetic polarizability. We show that thanks to their ability to rotate by field-induced torque under a rotating field, these microbeads can be employed in applications such as optical modulators and microrollers.

Aerodynamic Investigation on a Coaxial-Rotors Unmanned Aerial Vehicle of Bionic Chinese Parasol Seed.

Aerodynamic investigation of a bionic coaxial-rotors unmanned aerial vehicle (UAV) is performed. According to Chinese parasol seed features and flight requirements, the bionic conceptual design of a coaxial-rotors UAV is described. A solution procedure for the numerical simulation method, based on a multi-reference frame (MRF) model, is expressed, and a verification study is presented using the typical case. The aerodynamic design is conducted for airfoil, blade, and coaxial-rotors interference. The aerodynamic performance of the coaxial rotors is investigated by numerical simulation analysis. The rotor/motor integrated experiment verification is conducted to assess the performance of the coaxial-rotors UAV. The results indicate that the UAV has excellent aerodynamic performance and bionic configuration, allowing it to adapt to task requirements. The bionic UAV has a good cruise power load reach of 8.36 kg/kw, and the cruise flying thrust force is not less than 78 N at coaxial-rotor and rotor-balloon distance ratios of 0.39 and 1.12, respectively. It has the "blocks stability phenomenon" formed by the rotor downwash speed decreases and the balloon's additional negative pressure. The present method and the bionic configuration provide a feasible design and analysis strategy for coaxial-rotors UAVs.

Core-Alkynylated Fluorescent Flippers: Altered Ultrafast Photophysics to Track Thick Membranes.

Fluorescent flippers have been introduced as small-molecule probes to image membrane tension in living systems. This study describes the design, synthesis, spectroscopic and imaging properties of flippers that are elongated by one and two alkynes inserted between the push and the pull dithienothiophene domains. The resulting mechanophores combine characteristics of flippers, reporting on physical compression in the ground state, and molecular rotors, reporting on torsional motion in the excited state, to take their photophysics to new level of sophistication. Intensity ratios in broadened excitation bands from differently twisted conformers of core-alkynylated flippers thus report on mechanical compression. Lifetime boosts from ultrafast excited-state planarization and lifetime drops from competitive intersystem crossing into triplet states report on viscosity. In standard lipid bilayer membranes, core-alkynylated flippers are too long for one leaflet and tilt or extend into disordered interleaflet space, which preserves rotor-like torsional disorder and thus weak, blue-shifted fluorescence. Flipper-like planarization occurs only in highly ordered membranes of matching leaflet thickness, where they light up and selectively report on these thick membranes with red-shifted, sharpened excitation maxima, high intensity and long lifetime.

Cy3-Based Nanoviscosity Determination of Mucus: Effect of Mucus Collection Methods and Antibiotics Treatment.

The integrity of the protective mucus layer as a primary defense against pathogen invasion and microbial leakage into the intestinal epithelium can be compromised by the effects of antibiotics on the commensal microbiome. Changes in mucus integrity directly affect the solvent viscosity in the immediate vicinity of the mucin network, that is, the nanoviscosity, which in turn affects both biochemical reactions and selective transport. To assess mucus nanoviscosity, a reliable readout via the viscosity-dependent fluorescence lifetime of the molecular rotor dye cyanine 3 is established and nanoviscosities from porcine and murine ex vivo mucus are determined. To account for different mucin concentrations due to the removal of digestive residues during mucus collection, the power law dependence of mucin concentration on viscosity is used. The impact of antibiotics combinations (meropenem/vancomycin, gentamycin/ampicillin) on ex vivo intestinal mucus nanoviscosity is presented. The significant increase in viscosity of murine intestinal mucus after treatment suggests an effect of antibiotics on the microbiota that affects mucus integrity. This method will be a useful tool to assess how drugs, directly or indirectly, affect mucus integrity. Additionally, the method can be utilized to analyze the role of mucus nanoviscosity in health and disease, as well as in drug development.

Molecular Dynamics of Steroidal Rotors Probed by Theoretical, Spectroscopic and Dielectric Methods.

Our study focuses on molecular rotors with fast-moving rotators and their potential applications in the development of new amphidynamic crystals. Steroidal molecular rotors with a dipolar fluorine-substituted phenyl group as the rotator were synthesized and characterized. Three different rotors were investigated with varying numbers of fluorine atoms. A comprehensive analysis was performed using vibrational spectroscopy (Raman, FT-IR), electronic circular dichroism (ECD), and dielectric response to understand the behavior of the investigated model rotors. The results were supported by theoretical calculations using Density Functional Theory (DFT) methods. The angle-dependent polarized Raman spectra confirmed the crystallinity of the samples. Nearly frequency and temperature-independent permittivity suggest low-frequency librational motion of stators. An in-depth analysis of ECD spectra revealed high conformational flexibility in solution, resulting in low ECD effects, while in the solid-state with restricted rotation, significant ECD effects were observed. These findings shed light on the conformational behavior and potential applications of the studied steroidal molecular rotors.

Directed Graph Mapping exceeds Phase Mapping for the detection of simulated 2D meandering rotors in fibrotic tissue with added noise.

Cardiac arrhythmias such as atrial fibrillation (AF) are recognised to be associated with re-entry or rotors. A rotor is a wave of excitation in the cardiac tissue that wraps around its refractory tail, causing faster-than-normal periodic excitation. The detection of rotor centres is of crucial importance in guiding ablation strategies for the treatment of arrhythmia. The most popular technique for detecting rotor centres is Phase Mapping (PM), which detects phase singularities derived from the phase of a signal. This method has been proven to be prone to errors, especially in regimes of fibrotic tissue and temporal noise. Recently, a novel technique called Directed Graph Mapping (DGM) was developed to detect rotational activity such as rotors by creating a network of excitation. This research aims to compare the performance of advanced PM techniques versus DGM for the detection of rotors using 64 simulated 2D meandering rotors in the presence of various levels of fibrotic tissue and temporal noise. Four strategies were employed to compare the performances of PM and DGM. These included a visual analysis, a comparison of F2-scores and distance distributions, and calculating p-values using the mid-p McNemar test. Results indicate that in the case of low meandering, fibrosis and noise, PM and DGM yield excellent results and are comparable. However, in the case of high meandering, fibrosis and noise, PM is undeniably prone to errors, mainly in the form of an excess of false positives, resulting in low precision. In contrast, DGM is more robust against these factors as F2-scores remain high, yielding F2≥0.931 as opposed to the best PM F2≥0.635 across all 64 simulations.

Molecular Rotors for In Situ Viscosity Mapping during Evaporation of Confined Fluid Mixtures.

Numerous formulation processes of materials involve a drying step, during which evaporation of a solvent from a multicomponent liquid mixture, often confined in a thin film or in a droplet, leads to concentration and assembly of nonvolatile compounds. While the basic phenomena ruling evaporation dynamics are known, precise modeling of practical situations is hindered by the lack of tools for local and time-resolved mapping of concentration fields in such confined systems. In this article, the use of fluorescence lifetime imaging microscopy and of fluorescent molecular rotors is introduced as a versatile, in situ, and quantitative method to map viscosity and concentration fields in confined, evaporating liquids. More precisely, the cases of drying of a suspended liquid film and of a sessile droplet of mixtures of fructose and water are investigated. Measured viscosity and concentration fields allow characterization of drying dynamics, in agreement with simple modeling of the evaporation process.

Controlled synchronization of three co-rotating exciters based on a circular distribution in a vibratory system.

In this article, an engineering problem of three co-rotating exciters with the circular distribution in a vibrating system is investigated. The dynamical model constructed by the motion differential equations is established. By introducing the small parameter averaged method in the dynamic equation, the synchronization and stability conditions of the electromechanical coupling dynamical model is derived. To illustrate the necessity of the controlling method, the self-synchronization of the vibrating system is firstly analyzed with the theory, numerical simulations and experiments. With the self-synchronization results, it is indicated that the ellipse trajectory which is needed in the industry can't be realizefd by the self-synchronization motion of the vibrating system. And then, a fuzzy PID controlling method based on the master-slave controlling strategy is introduced in the vibrating system to realize the controlled synchronization. The Lyapunov stability criterion is given to certify the stability of the controlling system. Through some simulations and experiments, the effectiveness of controlled synchronization is illustrated in the discussion. Finally, the present work illuminates the feasibility and practicality for designing some new types of vibrating screens in the industry.

Polymer network comprised of steroidal rotors as promising storage material.

In this paper, we report a new generation of polymeric networks as potential functional material based on changes in molecular dynamics in the solid state. The material is obtained by free radical polymerization of a diacrylate derivative bearing a steroid (stator) and a 1,4-diethynyl-phenylene-d4 fragment (rotator). Polymer research using the PALS technique complements the knowledge about nanostructural changes occurring in the system in the temperature range -115 °C - +190 °C. It indicates the presence of two types of free nanovolumes in the system and the occurrence of phase transitions. The polymer is characterized using 1 H NMR, 2 H Solid Echo NMR, ATR-FTIR and Raman spectroscopies, thermal analysis, and porosimetry. It is proved that the applied procedure leads to the formation of a novel porous organic material containing multiple molecular rotors.

Molecular Rotors: Fluorescent Sensors for Microviscosity and Conformation of Biomolecules.

The viscosity and crowding of biological environment are considered vital for the correct cellular function, and alterations in these parameters are known to underly a number of pathologies including diabetes, malaria, cancer and neurodegenerative diseases, to name a few. Over the last decades, fluorescent molecular probes termed molecular rotors proved extremely useful for exploring viscosity, crowding, and underlying molecular interactions in biologically relevant settings. In this review, we will discuss the basic principles underpinning the functionality of these probes and will review advances in their use as sensors for lipid order, protein crowding and conformation, temperature and non-canonical nucleic acid structures in live cells and other relevant biological settings.

A Photoelectromagnetic 3D Metal-Organic Framework from Flexible Tetraarylethylene-Backboned Ligand and Dynamic Copper-Based Coordination Chemistry.

Porous frameworks that display dynamic responsiveness are of interest in the fields of smart materials, information technology, etc. In this work, a novel copper-based dynamic metal-organic framework [Cu3TTBPE6(H2O)2] (H4TTBPE = 1,1,2,2-tetrakis(4″-(1H-tetrazol-5-yl)-[1,1″-biphenyl]-4-yl)ethane), denoted as HNU-1, is reported which exhibits modulable photoelectromagnetic properties. Due to the synergetic effect of flexible tetraarylethylene-backboned ligands and diverse copper-tetrazole coordination chemistries, a complex 3D tunneling network is established in this MOF by the layer-by-layer staggered assembly of triplicate monolayers, showing a porosity of 59%. These features further make it possible to achieve dynamic transitions, in which the aggregate-state MOF can be transferred to different structural states by changing the chemical environment or upon heating while displaying sensitive responsiveness in terms of light absorption, photoluminescence, and magnetic properties.

Wireless Magnetoelectrochemical Induction of Rotational Motion.

Electromagnetically induced rotation is a key process of many technological systems that are used in daily life, especially for energy conversion. In this context, the Lorentz force-induced deviation of charges is a crucial physical phenomenon to generate rotation. Herein, they combine the latter with the concept of bipolar electrochemistry to design a wireless magnetoelectrochemical rotor. Such a device can be considered as a wet analog of a conventional electric motor. The main driving force that propels this actuator is the result of the synergy between the charge-compensating ion flux along a bipolar electrode and an external magnetic field applied orthogonally to the surface of the object. The trajectory of the wirelessly polarized rotor can be controlled by the orientation of the magnetic field relative to the direction of the global electric field, producing a predictable clockwise or anticlockwise motion. Fine-tuning of the applied electric field allows for addressing conducting objects having variable characteristic lengths.

Cyanoarylporphyrazine dyes: multimodal compounds for personalised photodynamic therapy.

Photodynamic therapy is known as an effective primary and adjuvant anticancer treatment. Compounds with improved properties or additional modalities are still needed to create an 'ideal' photosensitizer. In this article, we review cyanoarylporphyrazine dyes for photodynamic (anticancer) therapy that we have synthesised to date. The review provides information on the chemistry of cyanoarylporphyrazines, photophysical properties, cellular uptake features and the use of various carriers for selective delivery of cyanoarylporphyrazines to the tumour. The potential of cyanoarylporphyrazines as photodynamic anti-tumour agents also has been evaluated. The most interesting feature of cyanoarylporphyrazines is the dependence of the fluorescence quantum yield and excited state lifetime on the viscosity of the medium, which makes it possible to use them as viscosity sensors in photodynamic therapy. In the future, we expect that the unique combination of photosensitizer and viscosity sensor properties of cyanoarylporphyrazines will provide a tool for dosimetry and tailoring treatment regimens in photodynamic therapy to the individual characteristics of each patient.

Correlation of Plasma Membrane Microviscosity and Cell Stiffness Revealed via Fluorescence-Lifetime Imaging and Atomic Force Microscopy.

The biophysical properties of cells described at the level of whole cells or their membranes have many consequences for their biological behavior. However, our understanding of the relationships between mechanical parameters at the level of cell (stiffness, viscoelasticity) and at the level of the plasma membrane (fluidity) remains quite limited, especially in the context of pathologies, such as cancer. Here, we investigated the correlations between cells' stiffness and viscoelastic parameters, mainly determined via the actin cortex, and plasma membrane microviscosity, mainly determined via its lipid profile, in cancer cells, as these are the keys to their migratory capacity. The mechanical properties of cells were assessed using atomic force microscopy (AFM). The microviscosity of membranes was visualized using fluorescence-lifetime imaging microscopy (FLIM) with the viscosity-sensitive probe BODIPY 2. Measurements were performed for five human colorectal cancer cell lines that have different migratory activity (HT29, Caco-2, HCT116, SW 837, and SW 480) and their chemoresistant counterparts. The actin cytoskeleton and the membrane lipid composition were also analyzed to verify the results. The cell stiffness (Young's modulus), measured via AFM, correlated well (Pearson r = 0.93) with membrane microviscosity, measured via FLIM, and both metrics were elevated in more motile cells. The associations between stiffness and microviscosity were preserved upon acquisition of chemoresistance to one of two chemotherapeutic drugs. These data clearly indicate that mechanical parameters, determined by two different cellular structures, are interconnected in cells and play a role in their intrinsic migratory potential.

Formation of Highly Emissive Anthracene Excimers for Aggregation-Induced Emission/Self-Assembly Directed (Bio)imaging.

AIEgens have emerged as a promising alternative to molecular rotors in bioimaging applications. However, transferring the concept of aggregation-induced emission (AIE) from solution to living systems remains a challenge. Given the highly heterogeneous nature and the compartmentalization of the cell, different approaches are needed to control the self-assembly within the crowded intricate cellular environment. Herein, we report for the first time the self-assembly mechanism of an anthracene-guanidine derivative (AG) forming the rare and highly emissive T-shaped dimer in breast cancer cell lines as a proof of concept. This process is highly sensitive to the local environment in terms of polarity, viscosity, and/or water quantity that should enable the use of the AG as a fluorescence lifetime imaging biosensor for intracellular imaging of cellular structures and the monitoring of intracellular state parameters. Different populations of the monomer and T-shaped and π-π dimers were observed in the cell membrane, cytoplasm, and nucleoplasm, related to the local viscosity and presence of water. The T-shaped dimer is formed preferentially in the nucleus because of the higher density and viscosity compared to the cytoplasm. The present results should serve as a precursor for the development of new design strategies for molecular systems for a wide range of applications such as cell viscosity, density, or temperature sensing and imaging.

Atrial fibrillation activation patterns predict freedom from arrhythmias after catheter ablation: utility of ExTRa mapping™.

Background: Mechanisms underlying atrial fibrillation (AF) are widely complex and vary tremendously among individuals. Objectives: This retrospective study aimed to investigate the association between AF activation patterns and clinical outcomes post-ablation. Methods: Fifty-five AF patients (64.0 ± 12.9 years; 41 men; 17 paroxysmal) underwent bi-atrial endocardial driver mapping during AF pre-ablation with a real-time phase mapping system (ExTRa Mapping). The nonpassively activated ratio (%NP) of meandering rotors and multiple wavelets relative to the recording time was evaluated in 26 atrial segments [15 in the left atrium (LA) and 11 in the right atrium]. Irrespective of the mapping results, all patients underwent standard AF ablation via cryoballoons and/or radiofrequency catheters. Results: In a median follow-up interval of 27(14-30) months, 69.1% of patients were free from recurrent arrhythmias and antiarrhythmic drugs at one year post-procedure. Patients with recurrent AF were more likely to have non-paroxysmal AF, a significantly larger LA size, and higher LA maximal %NP(LAmax%NP) and LA anterior wall %NP(LAAW%NP) than those without recurrent AF. A multivariate Cox regression analysis showed that both an LAmax%NP (hazard ratio [HR] = 1.075; 95% confidence interval [CI] = 1.02-1.14, p = 0.012) and LAAW%NP (HR = 1.061; 95% CI = 1.01-1.11, p = 0.013) were independent predictors of atrial arrhythmia recurrence. The optimal cutoff points for the LAmax%NP and LAAW%NP for predicting AF recurrence were 64.5% and 60.0%, respectively. A Kaplan-Meier analysis demonstrated that both an LAmax%NP > 64.5% (p = 0.0062) and LAAW%NP > 60.0% (p = 0.014) were associated with more frequent AF recurrences. Conclusion: Baseline AF activation pattern mapping may aid in predicting freedom from arrhythmias after standard AF ablation procedures.

Giant Crystalline Molecular Rotors that Operate in the Solid State.

Molecular motion in the solid state is typically precluded by the highly dense environment, and only molecules with a limited range of sizes show such dynamics. Here, we demonstrate the solid-state rotational motion of two giant molecules, i.e., triptycene and pentiptycene, by encapsulating a bulky N-heterocyclic carbene (NHC) Au(I) complex in the crystalline media. To date, triptycene is the largest molecule (surface area: 245 Å2 ; volume: 219 Å3 ) for which rotation has been reported in the solid state, with the largest rotational diameter among reported solid-state molecular rotors (9.5 Å). However, the pentiptycene rotator that is the subject of this study (surface area: 392 Å2 ; volume: 361 Å3 ; rotational diameter: 13.0 Å) surpasses this record. Single-crystal X-ray diffraction analyses of both the developed rotors revealed that these possess sufficient free volume around the rotator. The molecular motion in the solid state was confirmed using variable-temperature solid-state 2 H spin-echo NMR studies. The triptycene rotor exhibited three-fold rotation, while temperature-dependent changes of the rotational angle were observed for the pentiptycene rotor.

Molecular Engineering to Boost the Photo-Oxidase Activity of Molecular Rotors in Colorimetric Sensing of Temperatures.

Some organic dyes and photosensitizers with strong visible absorption can behave as photo-responsive oxidase mimics. However, the relationship between the photo-oxidase activity and molecular structure remains unclear to date. In this work, a new type of photosensitizer with the characteristics of molecular rotors, namely DPPy, served as the molecular scaffold for further investigation. To adjust the photocatalytic oxidation ability, DAPy and CBPy were designed and synthesized based on the enhancement and diminishment of the intramolecular charge transfer (ICT) process, respectively. Kinetic studies revealed that DAPy and CBPy both exhibited highly efficient photo-activated oxidase-like activity with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate, which were in good accordance with their molecular engineering to promote either type I or type II reactive oxygen species (ROS) generation. Impressively a colorimetric method based on the visible light induced oxidase-like activity of molecular rotors was developed to determine the environmental temperature for the first time. Both DAPy and CBPy showed distinct sensitivities toward temperature as compared with several molecular rotors based on the typical fluorimetric detection. This work provides a new strategy for the application of molecular rotors to overcome the non-emissive challenge in temperature sensing.