Carole Aimé

Individualized Silica Nanohelices and Nanotubes : Tuning Inorganic Nanostructures Using Lipidic Self-Assemblies

Diverse chiral nanometric ribbons and tubules formed by self-assembly of organic amphiphilic molecules could be transcribed to inorganic nanostructures using a novel sol-gel transcription protocol with tetraethoxysilane (TEOS) in the absence of catalyst or cosolvent. By controlling parameters such as temperature or the concentration of the different reactants, we could finely tune the morphology of the inorganic nanostructures formed from organic templates. This fine-tuning has also been achieved upon controlling the kinetics of both organic assembly formation and inorganic polycondensation. The results presented herein show that the dynamic and versatile nature of the organic gels considerably enhances the tunability of inorganic materials with rich polymorphisms.

Determination of collagen fibril size via absolute measurements of second-harmonic generation signals

The quantification of collagen fibril size is a major issue for the investigation of pathological disorders associated with structural defects of the extracellular matrix. Second-harmonic generation microscopy is a powerful technique to characterize the macromolecular organization of collagen in unstained biological tissues. Nevertheless, due to the complex coherent building of this nonlinear optical signal, it has never been used to measure fibril diameter so far. Here we report absolute measurements of second-harmonic signals from isolated fibrils down to 30 nm diameter, via implementation of correlative second-harmonic-electron microscopy. Moreover, using analytical and numerical calculations, we demonstrate that the high sensitivity of this technique originates from the parallel alignment of collagen triple helices within fibrils and the subsequent constructive interferences of second-harmonic radiations. Finally, we use these absolute measurements as a calibration for ex vivo quantification of fibril diameter in the Descemets membrane of a diabetic rat cornea.

Molecular and supramolecular chirality in gemini-tartrate amphiphiles studied by electronic and vibrational circular dichroisms†

This contribution presents an application of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) to study the molecular and supramolecular chirality in assemblies of gemini-tartrate amphiphiles. Nonchiral dicationic n-2-n amphiphiles (n = 14-20) can self-organize into right- or left-handed structures upon interacting with chiral tartrate counterions. Micellar solutions can also be obtained for shorter alkyl chains (n = 12). First, the conformation of tartrate counterions has been investigated in various environments (micellar solutions and chiral ribbons). ECD and VCD spectra recorded in micellar solutions are independent from the solvent and from the nature of the cations (sodium, cetyl-trimethylammonium, or dimeric surfactant 12-2-12) used and are representative of the anticonformation of the tartrate dianions. On the other hand, drastic changes in the ECD and VCD spectra have been observed in multilayered chiral assemblies of 16-2-16 tartrate. These strong spectral modifications are associated with the chiral arrangement of the tartrate molecules at the surface of the bilayers. Moreover, chirality transfer from counterions to achiral amphiphiles has been clearly evidenced by VCD since circular dichroism has been observed on vibrations related to alkyl chains and gemini headgroups. Finally, ECD and VCD experiments were performed varying the enantiomeric excess of the tartrate. The ECD and VCD intensities do not vary linearly with the enantiomeric excess of the anion and different behaviors have been observed from the two spectroscopic methods: ECD intensities are correlated to the pitch of the ribbons, whereas the VCD intensities are correlated to the dimension of the chiral ribbons.

Biochemical investigation of the formation of three-dimensional networks from DNA-grafted large silica particles.

DNA is used to rationally build up networks of silica nanoparticles (SiNPs) based on the molecular recognition properties of complementary sequences. Network self-assembly is controlled from DNA covalently grafted at the surface of chemically modified SiNPs. Two strategies are compared, where grafted DNA sequences are designed in a three-strand system using noncomplementary sequences and an extra DNA linker, or in a two-strand approach for direct hybridization. In this paper, both systems are compared in terms of DNA hybridization stability, network size, and three-dimensional organization using a combination of dynamic light scattering and electron microscopy. The observed differences are discussed in terms of hybridization interactions between DNA sequences in particle-free systems through fluorescence, circular dichroism, and UV spectroscopy techniques.

In situ three-dimensional monitoring of collagen fibrillogenesis using SHG microscopy

We implemented in situ time-lapse Second Harmonic Generation (SHG) microscopy to monitor the three-dimensional (3D) self-assembly of collagen in solution. As a proof of concept, we tuned the kinetics of fibril formation by varying the pH and measured the subsequent exponential increase of fibril volume density in SHG images. We obtained significantly different time constants at pH = 6.5 ± 0.3 and at pH = 7.5 ± 0.3. Moreover, we showed that we could focus on the growth of a single isolated collagen fibril because SHG microscopy is sensitive to well-organized fibrils with diameter below the optical resolution. This work illustrates the potential of SHG microscopy for the rational design and characterization of collagen-based biomaterials.

Nucleotide-Promoted Morphogenesis in Amphiphile Assemblies: Kinetic Control of Micrometric Helix Formation†

Anionic nucleotides adenosine monophosphate or guanosine monophosphate interact with cationic vesicles, exchange with the counteranions of the amphiphiles in situ, and organize themselves at the membrane surfaces. Such organized nucleotides reciprocally transfer their chirality to membranes of nonchiral amphiphiles to induce the formation of right-handed micrometric helices on the time scale of hours. The kinetics of the nucleotide molecular organization and the formation of supramolecular helices was followed. We have shown that helix formation is a kinetic-dependent process that does not primarily result from ion exchange but from conformational reorganization and formation of weak interactions between confined nucleotides.

Reversible bioresponsive aptamer-based nanocomposites: ATP binding and removal from DNA-grafted silica nanoparticles

The bio-responsive reversible assembly of silica nanoparticles grafted with complementary DNA strands containing an ATP-sensitive aptamer sequence was studied. The optimal conditions for ATP-induced specific disassembly of the bionanocomposite network were identified, highlighting the existing competition between ATP/aptamer interactions and DNA duplex stability. A new, dialysis-based method for ATP removal was proposed, allowing partial re-formation of the initial DNA duplexes. Further disassembly was re-achieved by subsequent addition of ATP. These data constitute promising preliminary steps towards DNA-based fully reversible responsive bionanocomposite devices.

Fibrillogenesis from nanosurfaces: multiphoton imaging and stereological analysis of collagen 3D self-assembly dynamics.

The assembly of proteins into fibrillar structures is an important process that concerns different biological contexts, including molecular medicine and functional biomaterials. Engineering of hybrid biomaterials can advantageously provide synergetic interactions of the biopolymers with an inorganic component to ensure specific supramolecular organization and dynamics. To this aim, we designed hybrid systems associating collagen and surface-functionalized silica particles and we built a new strategy to investigate fibrillogenesis processes in such multicomponents systems, working at the crossroads of chemistry, physics and mathematics. The self-assembly process was investigated by bimodal multiphoton imaging coupling second harmonic generation (SHG) and 2 photon excited fluorescence (2PEF). The in-depth spatial characterization of the system was further achieved using the three-dimensional analysis of the SHG/2PEF data via mathematical morphology processing. Quantitation of collagen distribution around particles offers strong evidence that the chemically induced confinement of the protein on the silica nanosurfaces has a key influence on the spatial extension of fibrillogenesis. This new approach is unique in the information it can provide on 3D dynamic hybrid systems and may be extended to other associations of fibrillar molecules with optically responsive nano-objects.

Silica core–shell particles for the dual delivery of gentamicin and rifamycin antibiotics

Increasing bacterial resistance calls for the simultaneous delivery of multiple antibiotics. One strategy is to design a unique pharmaceutical carrier that is able to incorporate several drugs with different physico-chemical properties. This is highly challenging as it may require the development of compartmentalization approaches. Here we have prepared core-shell silica particles allowing for the dual delivery of gentamicin and rifamycin. The effect of silica particle surface functionalization on antibiotic sorption was first studied, enlightening the role of electrostatic and hydrophobic interactions. This in turn dictates the chemical conditions for shell deposition and further sorption of these antibiotics. In particular, the silica shell deposition was favored by the positively charged layer of gentamicin coating on the core particle surface. Shell modification by thiol groups finally allowed for rifamycin sorption. The antibacterial activity of the core-shell particles against Staphylococcus aureus and Pseudomonas aeruginosa demonstrated the dual release and action of the two antibiotics.

Preserving the spin transition properties of iron-triazole coordination polymers within silica-based nanocomposites

One dimensional iron(II) coordination polymers formed from 1,2,4-triazole bridging ligands are a unique class of spin-crossover materials (SCO). The integration of those coordination polymers into devices for practical applications remains a major challenge. Using a nanocomposite approach based on the control of coordination polymer interactions with chemically engineered silica particles, we show that we can achieve in situ gelation, while preserving the SCO properties of the solid state. Tuning the interface between the two phases of a composite provides a unique way to synergistically adjust the materials structure and the cooperativity associated with its transition properties. The strategy described here should allow for bridging the gap between soft and crystalline functional inorganic materials.