Out-of-Equilibrium Mechanical Disruption of ß-Amyloid-Like Fibers using Light-Driven Molecular Motors.

Artificial molecular motors have the potential to generate mechanical work on their environment by producing autonomous unidirectional motions when supplied with a source of energy. However, the harnessing of this mechanical work to subsequently activate various endoenergetic processes that can be useful in materials science remains elusive. Here, it is shown that by integrating a light-driven rotary motor through hydrogen bonds in a ß-amyloid-like structure forming supramolecular hydrogels, the mechanical work generated during the constant rotation of the molecular machine under UV irradiation is sufficient to disrupt the ß-amyloid fibers and to trigger a gel-to-sol transition at macroscopic scale. This melting of the gel under UV irradiation occurs 25 °C below the temperature needed to melt it by solely using thermal activation. In the dark, a reversible sol-gel transition is observed as the system fully recovers its original microstructure, thus illustrating the possible access to new kinds of motorized materials that can be controlled by advanced out-of-equilibrium thermodynamics.

Impact of polymorphism in oleogels of N-palmitoyl-L-phenylalanine.

Gels of edible oils, also called oleogels, are developed as alternative products of solid fats to limit the uptake of saturated and trans-unsaturated fats and lower the associated risk of coronary disease. The gelation of oils can be achieved with a low molecular weight organogelator (LMWO), a compound that self-assembles at low concentrations in a solid 3D network and provides the mixture its solid-like behavior. We have studied N-palmitoyl-L-phenylalanine (Palm-Phe), an endogenous compound (i.e. naturally present in the human body) as a model LMWO of rapeseed oil. Palm-Phe forms gels at a concentration of 1 wt% in rapeseed oil. We have studied the thermodynamic and mechanical behavior of the corresponding gels. As evidenced by DSC and rheology, this system exhibits two transitions upon heating, in addition to the sol-gel transition, a gel-gel transition between two polymorphic gels. The structural differences between both polymorphs were revealed using cryo-SEM, X-rays scattering, and FTIR experiments. The metastability of one of the polymorphs was proven by ageing and annealing experiments.

Matrix stiffness controls megakaryocyte adhesion, fibronectin fibrillogenesis, and proplatelet formation through Itgß3.

Megakaryocytes (MKs) are the precursor cells of platelets, located in the bone marrow (BM). Once mature, they extend elongated projections named proplatelets through sinusoid vessels, emerging from the marrow stroma into the circulating blood. Not all signals from the microenvironment that regulate proplatelet formation are understood, particularly those from the BM biomechanics. We sought to investigate how MKs perceive and adapt to modifications of the stiffness of their environment. Although the BM is one of the softest tissue of the body, its rigidification results from excess fibronectin (FN), and other matrix protein deposition occur upon myelofibrosis. Here, we have shown that mouse MKs are able to detect the stiffness of a FN-coated substrate and adapt their morphology accordingly. Using a polydimethylsiloxane substrate with stiffness varying from physiological to pathological marrow, we found that a stiff matrix favors spreading, intracellular contractility, and FN fibrils assembly at the expense of proplatelet formation. Itgb3, but not Itgb1, is required for stiffness sensing, whereas both integrins are involved in fibrils assembly. In contrast, soft substrates promote proplatelet formation in an Itgb3-dependent manner, consistent with the ex vivo decrease in proplatelet formation and the in vivo decrease in platelet number in Itgb3-deficient mice. Our findings demonstrate the importance of environmental stiffness for MK functions with potential pathophysiological implications during pathologies that deregulate FN deposition and modulate stiffness in the marrow.

Some Remarkable Rheological and Conducting Properties of Hybrid PVC Thermoreversible Gels/Organogels.

We report on investigations into the rheological properties of organogels prepared from triarylamine trisamide (TATA) and oligo phenylene vinylene (OPVOH) molecules in binary organogel gels and in ternary thermoreversible networks with poly vinyl chloride (PVC). In the case of OPVOH, we show that the modulus of the ternary gel is simply the sum of the modulus of each binary gel, corresponding to the so-called Voigt upper limit. In contrast, TATA/PVC ternary gels generally exceed the Voigt upper limit. In an attempt to account for this unexpected outcome, we hypothesized that a de-solvation process might occur in the PVC fibrils that possibly originates in the propensity of TATA molecules to form molecular compounds with the solvent. Finally, the conducting properties of TATA/solvent organogels and TAT/PVC/solvent reversible networks were measured. It was found that they strongly depend on the solvent type but are not significantly altered when PVC is present. Therefore, PVC gels can be made conducive by incorporating TATA fibers.

Palmitoylethanolamide gels edible oils.

Palmitoylethanolamide (PEA) is an endogenous compound with no adverse effect for oral intakes of a gram per day. We show that PEA gels edible oils at concentrations as low as 0.5 wt%. The elastic moduli values of the formed gels are 1400 Pa at 1 wt% and 9000 Pa at 2 wt%. The study of the gels by cryo-SEM, optical microscopy and WAXS show that PEA forms lamellar solid aggregates with widths of several tens of micrometers. Upon heating, the sample shows two transitions. The first one is the gel-to-sol transition, observed by rheology and defined by the switch from a solid to a liquid behavior. During this transition, the solid particles remain but do no longer form a network. The second transition, observed at higher temperature by DSC corresponds to the melting of the solid particles.

Investigation of an Organogel by Micro-Differential Scanning Calorimetry: Quantitative Relationship between the Shapes of the Thermograms and the Phase Diagram.

The phase diagrams of organogels are necessary for applications and fundamental aspects, for instance to understand their thermodynamics. Differential scanning calorimetry is one of the techniques implemented to map these diagrams. The thermograms of organogels upon heating show broad endotherms, increasing gradually to a maximum, at a temperature Tmax, and decreasing back to the baseline, sometimes 10 °C above. This broadening can lead to uncertainty in determining the molar enthalpies and the melting temperatures Tm of the gels. Herein, we have measured the thermograms of the 12-hydroxystearic acid/nitrobenzene gels for weight fractions ranging from 0.0015 to 0.04. Compared with transition temperatures measured by other techniques, the inflection points of the thermograms provide a measurement of Tm with less bias than Tmax. The phase diagram explains why the molar melting enthalpies derived from the thermograms for samples of low concentration are lower than expected. The shapes of the heat flows below the peak correlate quantitatively with the diagrams: after suitable correction and normalization, the integral curves superimpose with the phase diagram in their ascending branch and reach a plateau when the gel is fully melted. The shape of the thermograms upon cooling is also qualitatively explained within the frame of the diagrams.

Gel-to-gel non-variant transition of an organogel caused by polymorphism from nanotubes to crystallites.

An amide based gelator forms gels in trans-decalin. Below concentrations of 1 wt% the gels melt at temperatures varying with concentration. Above a concentration of 1 wt%, upon heating, the gel transforms into an opaque gel at an invariant temperature, and melts at higher temperature. The gel-to-gel transition is evidenced by several techniques: DSC, rheology, NMR, OM and turbidimetry. The phase diagram with the domain of the existence of both morphs was mapped by these techniques. Optical and electronic microscopy studies show that the first gel corresponds to the self-assembled nanotubes while the second gel is formed by crystalline fibers. The fibers are crystalline, as shown by the presence of Bragg peaks in the scattering curves. Both morphs correspond to a different H-bonding pattern as shown by FTIR. The first gel forms at a higher cooling rate, is metastable and transforms slowly into the second one. The second gel is stable. It forms at a low cooling rate, or by thermal annealing or aging of the first gel.

Covalently Trapped Triarylamine-Based Supramolecular Polymers.

C3 -Symmetric triarylamine trisamides (TATAs), decorated with three norbornene end groups, undergo supramolecular polymerization and further gelation by π-π stacking and hydrogen bonding of their TATA cores. By using subsequent ring-opening metathesis polymerization, these physical gels are permanently crosslinked into chemical gels. Detailed comparisons of the supramolecular stacks in solution, in the physical gel, and in the chemical gel states, are performed by optical spectroscopies, electronic spectroscopies, atomic force microscopy, electronic paramagnetic resonance spectroscopy, X-ray scattering, electronic transport measurements, and rheology. The results presented here clearly evidence that the core structure of the functional supramolecular polymers can be precisely retained during the covalent capture whereas the mechanical properties of the gels are concomitantly improved, with an increase of their storage modulus by two orders of magnitude.

Mechanical behaviour of contractile gels based on light-driven molecular motors.

The networking of individual artificial molecular motors into collective actuation systems is a promising approach for the design of active materials working out of thermodynamic equilibrium. Here, we report the first mechanical studies on active polymer gels built by integrating light-driven rotary molecular motors as reticulation units in polymer networks. We correlate the volume ratio before and after light irradiation with the change of the elastic modulus, and we reveal the universal maximum mechanical efficiency of such gels related to their critical overlap concentration before chemical reticulation. We also show the major importance of heterogeneities in the macroscopic contraction process and we confirm that these materials can increase their internal energy by the motorized winding of their polymer chains.

Protected Amino Acid-Based Hydrogels Incorporating Carbon Nanomaterials for Near-Infrared Irradiation-Triggered Drug Release.

Molecular gels formed by the self-assembly of low-molecular-weight gelators have received increasing interest because of their potential applications in drug delivery. In particular, the ability of peptides and amino acids to spontaneously self-assemble into three-dimensional fibrous network has been exploited in the development of hydrogels. In this context, we have investigated the capacity of binary mixtures of aromatic amino acid derivatives to form hydrogels. Carbon nanomaterials, namely oxidized carbon nanotubes or graphene oxide, were incorporated in the two most stable hydrogels, formed by Fmoc-Tyr-OH/Fmoc-Tyr(Bzl)-OH and Fmoc-Phe-OH/Fmoc-Tyr(Bzl)-OH, respectively. The structural and physical properties of these gels were assessed using microscopic techniques and rheology. Circular dichroism and molecular dynamics simulations demonstrated that the hydrogel formation was mainly driven by aromatic interactions. Finally, a model hydrophilic drug (l-ascorbic acid) was loaded into the hybrid hydrogels at a high concentration. Under near-infrared light irradiation, a high amount of drug was released triggered by the heat generated by the carbon nanomaterials, thus offering interesting perspectives for controlled drug delivery.

Variable temperature NMR of organogelators: the intensities of a single sample describe the full phase diagram.

Organogelators constitute a numerous class of compounds, able to form gels in organic solvents. Their phase diagrams are useful to understand their mechanisms of formation and their stability, but their mapping is often a tedious task. We show that liquid NMR can simplify and quicken the acquisition of phase diagrams. In liquid NMR spectra of organogels, the visible signals of the gelator represent only its soluble fraction. The intensities increase with temperature, until the gel melts. Suitable normalization of these intensities yields the solubility as a function of temperature, which is sufficient to map the phase diagram. We verified it experimentally with three organogelators, chosen because independent authors have previously mapped out their phase diagram by other techniques including DSC and rheology. We show that the curves obtained by NMR superimpose with these diagrams. A variable temperature NMR experiment with a single sample can yield the phase diagram with sensitivity of the order of 0.01 wt%.

Importance of environmental stiffness for megakaryocyte differentiation and proplatelet formation.

Megakaryocyte (MK) differentiation occurs within the bone marrow (BM), a complex 3-dimensional (3D) environment of low stiffness exerting local external constraints. To evaluate the influence of the 3D mechanical constraints that MKs may encounter in vivo, we differentiated mouse BM progenitors in methylcellulose (MC) hydrogels tuned to mimic BM stiffness. We found that MKs grown in a medium of 30- to 60-Pa stiffness more closely resembled those in the BM in terms of demarcation membrane system (DMS) morphological aspect and exhibited higher ploidy levels, as compared with MKs in liquid culture. Following resuspension in a liquid medium, MC-grown MKs displayed twice as much proplatelet formation as cells grown in liquid culture. Thus, the MC gel, by mimicking external constraints, appeared to positively influence MK differentiation. To determine whether MKs adapt to extracellular stiffness through mechanotransduction involving actomyosin-based modulation of the intracellular tension, myosin-deficient (Myh9-/-) progenitors were grown in MC gels. Absence of myosin resulted in abnormal cell deformation and strongly decreased proplatelet formation, similarly to features observed for Myh9-/- MKs differentiated in situ but not in vitro. Moreover, megakaryoblastic leukemia 1 (MKL1), a well-known actor in mechanotransduction, was found to be preferentially relocated within the nucleus of MC-differentiated MKs, whereas its inhibition prevented MC-mediated increased proplatelet formation. Altogether, these data show that a 3D medium mimicking BM stiffness contributes, through the myosin IIA and MKL1 pathways, to a more favorable in vitro environment for MK differentiation, which ultimately translates into increased proplatelet production.

Origin of Invariant Gel Melting Temperatures in the c-T Phase Diagram of an Organogel.

Binary c-T phase diagrams of organogelators in solvent are frequently simplified to two domains, gel and sol, even when the melting temperatures display two distinct regimes, an increase with T and a plateau. Herein, the c-T phase diagram of an organogelator in solvent is elucidated by rheology, DSC, optical microscopy, and transmitted light intensity measurements. We evidence a miscibility gap between the organogelator and the solvent above a threshold concentration, cL. In this domain the melting or the formation of the gel becomes a monotectic transformation, which explains why the corresponding temperatures are nonvariant above cL. As shown by further studies by variable temperature FTIR and NMR, different types of H-bonds drive both the liquid-liquid phase separation and the gelation.

Viscoelasticity of suspensions of magnetic particles in a polymer: effect of confinement and external field.

We study the suspensions of magnetic particles, the precursor state of magnetic gels and elastomers. We use magnetic particles with a permanent magnetization which is high enough to overcome thermal energy and low enough to guarantee a long live time of the sample. These particles form a space-filling structure at very low volume fractions (approximately 0.5 vol %), which modifies the viscoelastic response of the matrix significantly. In confined geometry the particles form clusters of a size that depends on the sample thickness. Even small external fields induce a strong anisotropy in the mechanical and optical properties of the suspension. The action of the applied magnetic field induces a gel-like response in one direction but leaves the other directions liquidlike. The viscosity is a very sensitive mechanical test for the anisotropy of the material. Light scattering data confirm our mechanical results.

Significant paternal contribution to the risk of small for gestational age.

OBJECTIVE: The aim of this study is to investigate both maternal and paternal contributions in the familial aggregation of small for gestational age. DESIGN: Nested case-control study. SETTING: Metropolitan area of Haguenau, France. POPULATION: Data were drawn from a French population-based maternity registry. After selection, 256 cases born either small for gestational age or average for gestational age were included. METHODS: Controlling for known pregnancy-related risk factors, logistic regression models were used to determine the risk of the child being small for gestational age, given that the mother, father or both were small for gestational age, and to examine interactions between maternal small for gestational age and pregnancy risk factors. MAIN OUTCOME MEASURES: Specifically, we investigate to what extent having either or both parents born small for gestational age increases the risk of small for gestational age in their offspring, after controlling for the established risk factors of small for gestational age and maternal and paternal characteristics. We also explore the extent to which the intergenerational predictors of small for gestational age may modify the effect of current pregnancy-related risk factors. RESULTS: The risk of a small for gestational age offspring was 4.7 times greater for mothers and 3.5 times greater for fathers who were small for gestational age, compared with average for gestational age counterparts. Furthermore, the risk of a small for gestational age offspring was 16.3 times greater when both parents were small for gestational age. No significant interactions between maternal small for gestational age and maternal smoking, hypertension or parity were observed. CONCLUSION: These results indicate that small for gestational age in both mother and father significantly influences the risk of their offspring being small for gestational age. While previous research has indicated that the birth outcome of the mother is an important determinant of the birth outcome of her offspring, these data indicate that the birth outcome of the father plays an equally critical role in determining fetal growth, strongly suggesting a genetic component in the familial aggregation of small for gestational age.