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Angiopoietins 1 and 2 (Ang1 and Ang2) regulate angiogenesis through their similar F‐domains by activating Tie2 receptors on endothelial cells. Despite the similarity in the underlying receptor‐binding interaction, the two angiopoietins have opposite effects: Ang1 induces phosphorylation of AKT, strengthens cell–cell junctions, and enhances endothelial cell survival while Ang2 can antagonize these effects, depending on cellular context. To investigate the molecular basis for the opposing effects, we examined the phenotypes of a series of computationally designed protein scaffolds presenting the Ang1 F‐domain in a wide range of valencies and geometries. We find two broad phenotypic classes distinguished by the number of presented F‐domains: Scaffolds presenting 3 or 4 F‐domains have Ang2‐like activity, upregulating pFAK and pERK but not pAKT, while scaffolds presenting 6, 8, 12, 30, or 60 F‐domains have Ang1‐like activity, upregulating pAKT and inducing migration and vascular stability. The scaffolds with 6 or more F‐domains display super‐agonist activity, producing stronger phenotypes at lower concentrations than Ang1. Tie2 super‐agonist nanoparticles reduced blood extravasation and improved blood–brain barrier integrity four days after a controlled cortical impact injury. Synopsis: An array of synthetic ligands designed computationally allows to precisely delineate the molecular basis of the Angiopoietin‐Tie2 pathway and the role of receptor oligomerization and transmembrane signaling. F‐domain valency determines the activation of pAKT, pERK, and pFAK downstream of Tie2.High valency F‐domain superagonists promote integrin colocalization and actin rearrangement.F‐domain scaffold superagonists promote vascular stabilization in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID‐19) pandemic has devastated families and disrupted healthcare, economies and societies across the globe. Molecular recognition agents that are specific for distinct viral proteins are critical components for rapid diagnostics and targeted therapeutics. In this work, we demonstrate the selection of novel DNA aptamers that bind to the SARS‐CoV‐2 spike glycoprotein with high specificity and affinity (<80 nM). Through binding assays and high resolution cryo‐EM, we demonstrate that SNAP1 (SARS‐CoV‐2 spike protein N‐terminal domain‐binding aptamer 1) binds to the S N‐terminal domain. We applied SNAP1 in lateral flow assays (LFAs) and ELISAs to detect UV‐inactivated SARS‐CoV‐2 at concentrations as low as 5×105 copies mL−1. SNAP1 is therefore a promising molecular tool for SARS‐CoV‐2 diagnostics. [ABSTRACT FROM AUTHOR]

The use of π‐conjugated polymers (CPs) in conductive hydrogels remains challenging due to the water‐insoluble nature of most CPs. Conjugated polyelectrolytes (CPEs) are promising alternatives because they have tunable electronic properties and high water‐solubility, but they are often difficult to synthesize and thus have not been widely adopted. Herein, we report the synthesis of an anionic poly(cyclopentadienylene vinylene) (aPCPV) from an insulating precursor under mild conditions and in high yield. Functionalized aPCPV is a highly water‐soluble CPE that exhibits low cytotoxicity, and we found that doping hydrogels with aPCPV imparts conductivity. We also anticipate that this synthetic strategy, due to its ease and high efficiency, will be widely used to create families of not‐yet‐explored π‐conjugated vinylene polymers. [ABSTRACT FROM AUTHOR]

Cellullar deficits are replenished within the central nervous system (CNS) by progenitors to maintain integrity and recover function after injury. NG2 proteoglycan-expressing progenitors replenish oligodendrocyte populations, but the nature of NG2 proteoglycan may not indicate a restricted population of progenitors. After injury, restorative spatiotemporal cues have the potential ability to regulate divergent fate-choices for NG2 progenitors, and NG2 progenitors are known to produce multiple cell types in vitro. Recent data suggest that NG2 expression is attenuated while protein levels remain high within injurious tissue; thus, NG2 expression is not static but transiently controlled in response to a dynamic interplay of environmental cues. Therefore, NG2 proteoglycan expression could label newly generated cells or be inherited by resident cell populations that produce oligodendrocytes for remyelination, astrocytes that provide trophic support and other cells that contribute to CNS function. [ABSTRACT FROM AUTHOR]