Assembling a new generation of radiopharmaceuticals with supramolecular theranostics
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Interface flexibility controls the nucleation and growth of supramolecular networks
Supramolecular networks are abundantly present in nature and, like crystalline materials, often develop from an initial nucleation site, followed by growth based on directional interactions between components. Traditionally, the binding strength and directionality of interactions is thought to dictate nucleation and crystal growth, whereas structural flexibility favours defects. Usually, macromonomers present multiple binding sites with relative intramolecular flexibility, but the effects of such flexibility on regulating network formation have been given little attention. Here we introduce the concept of ‘interface flexibility’ and demonstrate its critical importance in the nucleation and growth of supramolecular networks. As a model system, we use trisymmetric DNA-based macromonomers, which organize into hexagonal networks through weak π–π interactions at their tips. The directional nature and low spatial tolerance of π–π interactions mean that small shifts in orientation have a large effect on effective valency. We show that too much interface flexibility disrupts network formation, regardless of affinity. Tuning the interface flexibility greatly expands the available design space for synthetic supramolecular materials.
Stiff, lightweight, and programmable architectured pyrolytic carbon lattices via modular assembling
Recent advances in additive manufacturing have enabled the creation of three-dimensional (3D) architectured pyrolytic carbon (PyC) structures with ultrahigh specific strength and energy absorption capabilities. However, their scalability is limited by reduced strength at larger sizes. Here we introduce a modular assembling approach to scale up PyC lattice structures while retaining strength. Three assembling mechanisms—adhesive, Lego-adhesive, and mechanical interlocking—are explored, demonstrating notably increased specific compressive strength and modulus as size increases, driven by energy release from assembly joint fractures. Practical application is demonstrated by using assembled PyC lattices as the core of an aerospace sandwich structure, significantly enhancing indentation resistance compared to conventional aramid paper honeycomb core. The method also enables versatile designs, including curved structures for space debris protection and bio-scaffold applications. This scalable approach offers a promising pathway for integrating PyC structures into large-scale engineering applications requiring superior mechanical properties and programmability in complicated shape design.
A globular protein exhibits rare phase behavior and forms chemically regulated orthogonal condensates in cells
Proteins with chemically regulatable phase separation are of great interest in the fields of biomolecular condensates and synthetic biology. Intrinsically disordered proteins (IDPs) are the dominating building blocks of biomolecular condensates which often lack orthogonality and small-molecule regulation desired to create synthetic biomolecular condensates or membraneless organelles (MLOs). Here, we discover a well-folded globular protein, lipoate-protein ligase A (LplA) from E. coli involved in lipoylation of enzymes essential for one-carbon and energy metabolisms, that exhibits structural homomeric oligomerization and a rare LCST-type reversible phase separation in vitro. In both E. coli and human U2OS cells, LplA can form orthogonal condensates, which can be specifically dissolved by its natural substrate, the small molecule lipoic acid and its analogue lipoamide. The study of LplA phase behavior and its regulatability expands our understanding and toolkit of small-molecule regulatable protein phase behavior with impacts on biomedicine and synthetic biology.
Chemical linkers switch triglycerol detergents from bacterial protein purification to mild antibiotic amplification
Non-ionic detergents enable the investigation of cell membranes, including biomolecule purification and drug delivery. The question of whether non-ionic detergents associated with satisfying protein yields following extraction and affinity purification of proteins from lysed E. coli membranes can amplify antibiotics on whole-cell E. coli remains to be addressed. We unlock the modular chemistry of linear triglycerol detergents to reveal that more polar, non-ionic detergents that form globular micelles work better in amplifying antimicrobial activities of antibiotics than in purifying the membrane proteins mechanosensitive channel and aquaporin Z. Less polar detergents that form worm-like micelles indicate poor performances in both applications. With chromatography we demonstrate how fine-tuning the polarity of chemical linkers between detergent headgroups and tails can switch the utility of detergents from protein purification to antibiotic amplification. We anticipate our findings to be a starting point for structure-property studies to better understand detergent designs in supramolecular chemistry and membrane research.
Anthropogenic organic aerosol in Europe produced mainly through second-generation oxidation
Exposure to anthropogenic atmospheric aerosol is a major health issue, causing several million deaths per year worldwide. The oxidation of aromatic hydrocarbons from traffic and wood combustion is an important anthropogenic source of low-volatility species in secondary organic aerosol, especially in heavily polluted environments. It is not yet established whether the formation of anthropogenic secondary organic aerosol involves mainly rapid autoxidation, slower sequential oxidation steps or a combination of the two. Here we reproduced a typical urban haze in the ‘Cosmics Leaving Outdoor Droplets’ chamber at the European Organization for Nuclear Research and observed the dynamics of aromatic oxidation products during secondary organic aerosol growth on a molecular level to determine mechanisms underlying their production and removal. We demonstrate that sequential oxidation is required for substantial secondary organic aerosol formation. Second-generation oxidation decreases the products’ saturation vapour pressure by several orders of magnitude and increases the aromatic secondary organic aerosol yields from a few percent to a few tens of percent at typical atmospheric concentrations. Through regional modelling, we show that more than 70% of the exposure to anthropogenic organic aerosol in Europe arises from second-generation oxidation.
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