Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid-Spermine Conjugates.

Natural and abundant plant triterpenoids are attractive starting materials for the synthesis of conformationally rigid and chiral building blocks for functional soft materials. Here, we report the rational design of three oleanolic acid-triazole-spermine conjugates, containing either one or two spermine units in the target molecules, using the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The resulting amphiphile-like molecules 2 and 3, bearing just one spermine unit in the respective molecules, self-assemble into highly entangled fibrous networks leading to gelation at a concentration as low as 0.5% in alcoholic solvents. Using step-strain rheological measurements, we show rapid self-recovery (up to 96% of the initial storage modulus) and sol ⇔ gel transition under several cycles. Interestingly, rheological flow curves reveal the thixotropic behavior of the gels. To the best of our knowledge, this kind of behavior was not shown in the literature before, neither for a triterpenoid nor for its derivatives. Conjugate 4, having a bolaamphiphile-like structure, was found to be a nongelator. Our results indicate that the position and number of spermine units alter the gelation properties, gel strength, and their self-assembly behavior. Preliminary cytotoxicity studies of the target compounds 2-4 in four human cancer cell lines suggest that the position and number of spermine units affect the biological activity. Our results also encourage exploring other triterpenoids and their derivatives as sustainable, renewable, and biologically active building blocks for multifunctional soft organic nanomaterials.

UV-Triggered On-Demand Temperature-Responsive Reversible and Irreversible Gelation of Cellulose Nanocrystals.

We show ionically cross-linked, temperature-responsive reversible or irreversible hydrogels of anionic cellulose nanocrystals (CNCs) and methacrylate terpolymers by mixing them homogeneously in the initially charge-neutral state of the polymer, which was subsequently switched to be cationic by cleaving side groups by UV irradiation. The polymer is a random terpolymer poly(di(ethylene glycol) methyl ether methacrylate)-rnd-poly(oligo(ethylene glycol) methyl ether methacrylate)-rnd-poly(2-((2-nitrobenzyl)oxycarbonyl)aminoethyl methacrylate), that is, PDEGMA-rnd-POEGMA-rnd-PNBOCAEMA. The PDEGMA and POEGMA repeating units lead to a lower critical solution temperature (LCST) behavior. Initially, homogeneous aqueous mixtures are obtained with CNCs, and no gelation is observed even upon heating to 60 °C. However, upon UV irradiation, the NBOCAEMAs are transformed to cationic 2-aminoethyl methacrylate (AEMA) groups, as 2-nitrobenzaldehyde moieties are cleaved. The resulting mixtures of anionic CNC and cationic PDEGMA-rnd-POEGMA-rnd-PAEMA show gelation for sufficiently high polymer fractions upon heating to 60 °C due to the interplay of ionic interactions and LCST. For short heating times, the gelation is thermoreversible, whereas for long enough heating times, irreversible gels can be obtained, indicating importance of kinetic aspects. The ionic nature of the cross-linking is directly shown by adding NaCl, which leads to gel melting. In conclusion, the optical triggering of the polymer ionic interactions in combination with its LCST phase behavior allows a new way for ionic nanocellulose hydrogel assemblies.

Self-healing, luminescent metallogelation driven by synergistic metallophilic and fluorine-fluorine interactions.

Square planar platinum(ii) complexes are attractive building blocks for multifunctional soft materials due to their unique optoelectronic properties. However, for soft materials derived from synthetically simple discrete metal complexes, achieving a combination of optical properties, thermoresponsiveness and excellent mechanical properties is a major challenge. Here, we report the rapid self-recovery of luminescent metallogels derived from platinum(ii) complexes of perfluoroalkyl and alkyl derivatives of terpyridine ligands. Using single crystal X-ray diffraction studies, we show that the presence of synergistic platinum-platinum (PtPt) metallopolymerization and fluorine-fluorine (FF) interactions are the major driving forces in achieving hierarchical superstructures. The resulting bright red gels showed the presence of highly entangled three-dimensional networks and helical nanofibres with both (P and M) handedness. The gels recover up to 87% of their original storage modulus even after several cycles under oscillatory step-strain rheological measurements showing rapid self-healing. The luminescence properties, along with thermo- and mechanoresponsive gelation, provide the potential to utilize synthetically simple discrete complexes in advanced optical materials.

Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer.

Breast cancer is now globally the most frequent cancer and leading cause of women's death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.

Strain Stiffening and Negative Normal Force of Agarose Hydrogels.

Inspired by the specific strain stiffening and negative normal force phenomena in several biological networks, herein, we show strain stiffening and negative normal force in agarose hydrogels. We use both pre-strain and strain amplitude sweep protocols in dynamic rheological measurements where the gel slip was suppressed by the in situ gelation in the cross-hatched parallel plate rheometer geometry. Within the stiffening region, we show the scaling relation for the differential modulus K ∝ σ1, where σ is stress. The strain at the onset of stiffening is almost constant throughout the concentration range. The gels show negative apparent normal stress difference when sheared as a result of the gel contraction. The pore size of the hydrogel is large enough to allow water to move with respect to the network to balance the pressure difference caused by the hoop stress. The rheological analysis together with scanning electron microscopy suggests that the agarose gels can be described using subisostatic athermal network models where the connectivity dictates the stiffening behavior. Therefore, the simple agarose gels appear to capture several of the viscoelastic properties, which were previously thought to be characteristic to biological protein macromolecules.

Strain-Stiffening of Agarose Gels.

Strain-stiffening is one of the characteristic properties of biological hydrogels and extracellular matrices, where the stiffness increases upon increased deformation. Whereas strain-stiffening is ubiquitous in protein-based materials, it has been less observed for polysaccharide and synthetic polymer gels. Here we show that agarose, that is, a common linear polysaccharide, forms helical fibrillar bundles upon cooling from aqueous solution. The hydrogels with these semiflexible fibrils show pronounced strain-stiffening. However, to reveal strain-stiffening, suppressing wall slippage turned as untrivial. Upon exploring different sample preparation techniques and rheological architectures, the cross-hatched parallel plate geometries and in situ gelation in the rheometer successfully prevented the slippage and resolved the strain-stiffening behavior. Combining with microscopy, we conclude that strain-stiffening is due to the semiflexible nature of the agarose fibrils and their geometrical connectivity, which is below the central-force isostatic critical connectivity. The biocompatibility and the observed strain-stiffening suggest the potential of agarose hydrogels in biomedical applications.

Bipyridine based metallogels: an unprecedented difference in photochemical and chemical reduction in the in situ nanoparticle formation.

Metal co-ordination induced supramolecular gelation of low molecular weight organic ligands is a rapidly expanding area of research due to the potential in creating hierarchically self-assembled multi-stimuli responsive materials. In this context, structurally simple O-methylpyridine derivatives of 4,4'-dihydroxy-2,2'-bipyridine ligands are reported. Upon complexation with Ag(i) ions in aqueous dimethyl sulfoxide (DMSO) solutions the ligands spontaneously form metallosupramolecular gels at concentrations as low as 0.6 w/v%. The metal ions induce the self-assembly of three dimensional (3D) fibrillar networks followed by the spontaneous in situ reduction of the Ag-centers to silver nanoparticles (AgNPs) when exposed to daylight. Significant size and morphological differences of the AgNP's was observed between the standard chemical and photochemical reduction of the metallogels. The gelation ability, the nanoparticle formation and rheological properties were found to be depend on the ligand structure, while the strength of the gels is affected by the water content of the gels.