Supramolecular fibrillation in coacervates and other confined systems towards biomimetic function.

As in natural cytoskeletons, the cooperative assembly of fibrillar networks can be hosted inside compartments to engineer biomimetic functions, such as mechanical actuation, transport, and reaction templating. Coacervates impose an optimal liquid-liquid phase separation within the aqueous continuum, functioning as membrane-less compartments that can organise such self-assembling processes as well as the exchange of information with their environment. Furthermore, biological fibrillation can often be controlled or assisted by intracellular compartments. Thus, the reconstitution of analogues of natural filaments in simplified artificial compartments, such as coacervates, offer a suitable model to unravel, mimic, and potentially exploit cellular functions. This perspective summarises the latest developments towards assembling fibrillar networks under confinement inside coacervates and related compartments, including a selection of examples ranging from biological to fully synthetic monomers. Comparative analysis between coacervates, lipid vesicles, and droplet emulsions showcases the interplay between supramolecular fibres and the boundaries of the corresponding compartment. Combining inspiration from natural systems and the custom properties of tailored synthetic fibrillators, rational monomer and compartment design will contribute towards engineering increasingly complex and more realistic artificial protocells.

Self-assembly of cyclic peptide monolayers by hydrophobic supramolecular hinges.

Supramolecular polymerisation of two-dimensional (2D) materials requires monomers with non-covalent binding motifs that can control the directionality of both dimensions of growth. A tug of war between these propagation forces can bias polymerisation in either direction, ultimately determining the structure and properties of the final 2D ensemble. Deconvolution of the assembly dynamics of 2D supramolecular systems has been widely overlooked, making monomer design largely empirical. It is thus key to define new design principles for suitable monomers that allow the control of the direction and the dynamics of two-dimensional self-assembled architectures. Here, we investigate the sequential assembly mechanism of new monolayer architectures of cyclic peptide nanotubes by computational simulations and synthesised peptide sequences with selected mutations. Rationally designed cyclic peptide scaffolds are shown to undergo hierarchical self-assembly and afford monolayers of supramolecular nanotubes. The particular geometry, the rigidity and the planar conformation of cyclic peptides of alternating chirality allow the orthogonal orientation of hydrophobic domains that define lateral supramolecular contacts, and ultimately direct the propagation of the monolayers of peptide nanotubes. A flexible 'tryptophan hinge' at the hydrophobic interface was found to allow lateral dynamic interactions between cyclic peptides and thus maintain the stability of the tubular monolayer structure. These results unfold the potential of cyclic peptide scaffolds for the rational design of supramolecular polymerisation processes and hierarchical self-assembly across the different dimensions of space.

Next-generation MRI scanner designed for ultra-high-resolution human brain imaging at 7 Tesla.

To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.

Bottom-up supramolecular assembly in two dimensions.

The self-assembly of molecules in two dimensions (2D) is gathering attention from all disciplines across the chemical sciences. Attracted by the interesting properties of two-dimensional inorganic analogues, monomers of different chemical natures are being explored for the assembly of dynamic 2D systems. Although many important discoveries have been already achieved, great challenges are still to be addressed in this field. Hierarchical multicomponent assembly, directional non-covalent growth and internal structural control are a just a few of the examples that will be discussed in this perspective about the exciting present and the bright future of two-dimensional supramolecular assemblies.

A bacterial endosymbiont of the fungus Rhizopus microsporus drives phagocyte evasion and opportunistic virulence.

Opportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitous in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this and the evolutionary drivers underlying the acquisition of virulence mechanisms are poorly understood. Here, we show that a clinical isolate of Rhizopus microsporus contains a Ralstonia pickettii bacterial endosymbiont required for virulence in both zebrafish and mice and that this endosymbiosis enables the secretion of factors that potently suppress growth of the soil amoeba Dictyostelium discoideum, as well as their ability to engulf and kill other microbes. As amoebas are natural environmental predators of both bacteria and fungi, we propose that this tri-kingdom interaction contributes to establishing endosymbiosis and the acquisition of anti-phagocyte activity. Importantly, we show that this activity also protects fungal spores from phagocytosis and clearance by human macrophages, and endosymbiont removal renders the fungal spores avirulent in vivo. Together, these findings describe a new role for a bacterial endosymbiont in Rhizopus microsporus pathogenesis in animals and suggest a mechanism of virulence acquisition through environmental interactions with amoebas.

Cyclization and Self-Assembly of Cyclic Peptides.

Cyclic peptides are a fascinating class of molecules that can be programmed to fold or self-assemble into diverse mono- and multidimensional structures with potential applications in biomedicine, nanoelectronics, or catalysis. Herein we describe on-resin procedures to carry out head-to-tail peptide cyclization based on orthogonal protected linear structures. We also present essential characterization tools for obtaining dynamic and structural information, including the visualization cyclic peptide assembly into nanotubes (AFM, TEM) as well as the use of fluorescence microscopy.

Supramolecular fibrillation of peptide amphiphiles induces environmental responses in aqueous droplets.

One-dimensional (1D) supramolecular polymers are commonly found in natural and synthetic systems to prompt functional responses that capitalise on hierarchical molecular ordering. Despite amphiphilic self-assembly being significantly studied in the context of aqueous encapsulation and autopoiesis, very little is currently known about the physico-chemical consequences and functional role of 1D supramolecular polymerisation confined in aqueous compartments. Here, we describe the different phenomena that resulted from the chemically triggered supramolecular fibrillation of synthetic peptide amphiphiles inside water microdroplets. The confined connection of suitable dormant precursors triggered a physically autocatalysed chemical reaction that resulted in functional environmental responses such as molecular uptake, fusion and chemical exchange. These results demonstrate the potential of minimalistic 1D supramolecular polymerisation to modulate the behaviour of individual aqueous entities with their environment and within communities.

Sequence Decoding of 1D to 2D Self-Assembling Cyclic Peptides.

The inherent ability of peptides to self-assemble with directional and rationally predictable interactions has fostered a plethora of synthetic two-dimensional (2D) supramolecular biomaterials. However, the design of peptides with hierarchical assembly in different dimensions across mesoscopic lengths remains a challenging task. We here describe the structural exploration of a d/l-alternating cyclic octapeptide capable of assembling one-dimensional (1D) nanotubes in water, which subsequently pack laterally to form giant 2D nanosheets up to 500 µm long with a constant 3.2 nm thickness. Specific amino acid mutations allowed the mapping of structure-assembly relationships that determine 2D self-assembly. Nine peptide modifications were studied, revealing key features in the peptide sequence that nanosheets tolerated, while a total of three peptide variants included modifications that compromised their 2D arrangement. These lessons will serve as guide and inspiration for new 2D supramolecular peptide designs.

1D to 2D Self Assembly of Cyclic Peptides.

Despite recent developments in two-dimensional self-assembly, most supramolecular 2D materials are assembled by tedious methodologies, with complex surface chemistry and small sizes. We here report d/l-alternating cyclic peptides that undergo one-dimensional self-assembly into amphiphilic nanotubes, which subsequently arrange as tubular bilayers to form giant nanosheets in the mesoscale. Reversible transitions between the assembled, dispersed, and aggregated states of these nanosheets can be triggered by external stimuli. The characteristic flexibility, defined chemical topology, and length scale of these nanosheets set a clear distinction between this new supramolecular architecture and previously reported 2D nanostructures. The sequential 1D-to-2D self-assembly of peptides described here provides a conceptually new approach to achieve two-dimensional materials with hierarchical organization. These giant nanosheets represent one of the largest 2D supramolecular materials ever made, with potential application as long-range molecular transporters, responsive surfaces, and (bio)sensors.