We report the formation of cylindrical micelles, sheet-like micelles, tubular micelles, as well as polymer vesicles by a new series of amphiphilic linear-dendritic block-copolymers (BCs). The BCs, noted as PEGm-AZOn, are composed of poly(ethylene glycol) (PEG) chains of different molecular weights as hydrophilic blocks and the first four generations of azobenzene-containing dendrons based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) as hydrophobic blocks (m represents the degree of polymerization of PEG, and n is the number of azobenzene units at the periphery of dendron). The polymeric aggregates were formed by adding water to solutions of the BCs in dioxane. The micellar dispersions in water were finally obtained by removing dioxane via dialysis against water. The morphology of the micellar self-assemblies was studied by transmission electron microscopy (TEM), cryo-electron microscopy (cryo-TEM), and atomic force microscopy (AFM). A generation-dependent aggregation behavior was found for the series of BCs PEG45-AZOn. Core-shell structured nanofibers with an inner diameter of 8 nm were observed for the copolymer PEG45-AZO2 (hydrophilic/hydrophobic weight ratio equal to 67/33). Lyotropic liquid crystalline behavior was detected for the aqueous solution of the nanofibers. The coexistence of sheet-like aggregates and tubular micelles was detected for the copolymer PEG45-AZO8 in which the number of cyanoazobenzene units is increased to 8 (hydrophilic/hydrophobic weight ratio equal to 33/67). The tubular micelles could be intermediates in the sheet-like aggregate-to-vesicle transition. Polymer vesicles (polymersomes) with a diameter in the range 300-800 nm were observed for the copolymer PEG45-AZO16 (hydrophilic/hydrophobic weight ratio equal to 20/80). The membrane of the sheet-like aggregates, tubular micelles, and polymersomes was shown to have a bilayer structure, as revealed by cryo-TEM. UV illumination of the aqueous polymersome dispersion induced the formation of wrinkles in the vesicle membrane, thus showing that this type of polymeric aggregate is photoresponsive.

Physiological variability manifests itself via differences in physiological function between individuals of the same species, and has crucial implications in disease progression and treatment. Despite its importance, physiological variability has traditionally been ignored in experimental and computational investigations due to averaging over samples from multiple individuals. Recently, modelling frameworks have been devised for studying mechanisms underlying physiological variability in cardiac electrophysiology and pro-arrhythmic risk under a variety of conditions and for several animal species as well as human. One such methodology exploits populations of cardiac cell models constrained with experimental data, or experimentally-calibrated populations of models. In this review, we outline the considerations behind constructing an experimentally-calibrated population of models and review the studies that have employed this approach to investigate variability in cardiac electrophysiology in physiological and pathological conditions, as well as under drug action. We also describe the methodology and compare it with alternative approaches for studying variability in cardiac electrophysiology, including cell-specific modelling approaches, sensitivity-analysis based methods, and populations-of-models frameworks that do not consider the experimental calibration step. We conclude with an outlook for the future, predicting the potential of new methodologies for patient-specific modelling extending beyond the single virtual physiological human paradigm.

AimsHuman atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR) and chronic atrial fibrillation (cAF) patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP) recorded in 363 patients both under SR and cAF conditions.Methods and ResultsHuman AP recordings in atrial trabeculae (n = 469) from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in GK1, GKur and Gto, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in IK1 and INaK underlies variability in APD90, variability in IKur, ICaL and INaK modulates variability in APD50 and combined variability in Ito and IKur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by IK1 and either INaK or INaCa depending on the model.ConclusionExperimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP duration and morphology in SR versus cAF.

A new and efficient photopolymer for the recording of volume holograms is presented. The material comprises a mixture of UV‐sensitive acrylates and grafted titanium dioxide nanoparticles with an average size of 4 nm. We report the formation of holographic gratings with refractive‐index modulation amplitudes of up to 15.5 × 10–3—an improvement of more than a factor of four over the base material without nanoparticles—while maintaining a low level of scattering and a high transparency in the visible‐wavelength range. The influence of the composition of the acrylate system on the final properties of the holographic material is also investigated and discussed. The presence of multifunctional monomers favors the compositional segregation of the different components, while the addition of monofunctional acrylate, highly compatible with the grafting of the nanoparticles, favors the dilution of these nanoparticles.

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Photoembossing is a solvent‐free photolithographic technique for the production of polymeric relief microstructures (see Figure). A combinatorial methodology to explore the influence of different parameters (e.g., processing temperature, binder content, photoinitiator content) on the resultant relief structure is presented using an acrylate‐based model system. Results are discussed in the framework of a diffusion‐polymerization model.

We report here the synthesis of a series of new photoaddressable linear-dendritic diblock copolymers composed of poly(ethylene glycol) (PEG) and the first four generations of dendritic aliphatic polyesters based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) functionalized at the periphery with mesogenic and photochromic cyanazobenzene units. The dendritic block was synthesized through a doublestage convergent approach starting from the 2-azidoethyl ester of bis-MPA. Subsequent functionalization of the periphery allowed us to obtain liquid crystalline azodendrons bearing an azide group at the focal point. Finally, the block copolymers (BCs) were obtained by Huisgen's 1,3-dipolar cycloaddition (click chemistry) between the azo-dendrons and an alkyne-functionalized PEG. The chemical structure and low polydispersity of the BCs were checked by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FT-IR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and gel permeation chromatography (GPC). Liquid crystalline properties were analyzed by differential scanning calorimetry (DSC) and polarized-light optical microscopy (POM). The azodendrons showed a smectic phase over a broad temperature range. Mesomorphism was also detected for the BCs except for the BC bearing two cyanoazobenzene units. X-ray diffraction (XRD) experiments demonstrated the lamellar nanosegregation of the diblock copolymers. The lamellar nature of the morphology was also confirmed by transmission electron microscopy (TEM) measurements. Birefringence was induced using 488 nm linearly polarized light on thin films of the BC bearing 16 cyanoazobenzene units under different irradiation conditions. Stable values of the in-plane order parameter up to 0.56 were obtained for this material.

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