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Nanomaterial‐induced endothelial leakiness (NanoEL) is an interfacial phenomenon denoting the paracellular transport of nanoparticles that is pertinent to nanotoxicology, nanomedicine and biomedical engineering. While the NanoEL phenomenon is complementary to the enhanced permeability and retention effect in terms of their common applicability to delineating the permeability and behavior of nanoparticles in tumoral environments, these two effects significantly differ in scope, origin, and manifestation. In the current study, the descriptors are fully examined of the NanoEL phenomenon elicited by generic citrate‐coated gold nanoparticles (AuNPs) of changing size and concentration, from microscopic gap formation and actin reorganization down to molecular signaling pathways and nanoscale interactions of AuNPs with VE‐cadherin and its intra/extracellular cofactors. Employing synergistic in silico methodologies, for the first time the molecular and statistical mechanics of cadherin pair disruption, especially in response to AuNPs of the smallest size and highest concentration are revealed. This study marks a major advancement toward establishing a comprehensive NanoEL framework for complementing the understanding of the transcytotic pathway and for guiding the design and application of future nanomedicines harnessing the myriad functions of the mammalian vasculature.

The gut–brain axis has attracted increasing attention in recent years, fueled by accumulating symptomatic, physiological, and pathological findings. In this study, the aggregation and toxicity of amyloid beta (Aβ), the pathogenic peptide associated with Alzheimer's disease (AD), seeded by FapC amyloid fragments (FapCS) ofPseudomonas aeruginosathat colonizes the gut microbiome through infections are examined. FapCS display favorable binding with Aβand a catalytic capacity in seeding the peptide amyloidosis. Upon seeding, twisted Aβfibrils assume a much‐shortened periodicity approximating that of FapC fibrils, accompanied by a 37% sharp rise in the fibrillar diameter, compared with the control. The robust seeding capacity for Aβby FapCS and the biofilm fragments derived fromP. aeruginosaentail abnormal behavior pathology and immunohistology, as well as impaired cognitive function of zebrafish. Together, the data offer the first concrete evidence of structural integration and inheritance in peptide cross‐seeding, a crucial knowledge gap in understanding the pathological correlations between different amyloid diseases. The catalytic role of infectious bacteria in promoting Aβamyloidosis may be exploited as a potential therapeutic target, while the altered mesoscopic signatures of Aβfibrils may serve as a prototype for molecular assembly and a biomarker for screening bacterial infections in AD.

Amyloidosis is a biophysical phenomenon of protein aggregation with biological and pathogenic implications. Among the various strategies developed to date, nanomaterials and multifunctional nanocomposites possessing certain structural and physicochemical traits are promising candidates for mitigating amyloidosis in vitro and in vivo. The mechanisms underpinning protein aggregation and toxicity are introduced, and opportunities in materials science to drive this interdisciplinary field forward are highlighted. Advancement of this emerging frontier hinges on exploitation of protein self‐assembly and interactions of amyloid proteins with nanoparticles, intracellular and extracellular proteins, chaperones, membranes, organelles, and biometals.

The self‐assembly of human islet amyloid polypeptide (hIAPP) into β‐sheet‐rich nanofibrils is associated with the pathogeny of type 2 diabetes. Soluble hIAPP is intrinsically disordered with N‐terminal residues 8–17 as α‐helices. To understand the contribution of the N‐terminal helix to the aggregation of full‐length hIAPP, here the oligomerization dynamics of the hIAPP fragment 8–20 (hIAPP8‐20) are investigated with combined computational and experimental approaches. hIAPP8‐20 forms cross‐β nanofibrils in silico from isolated helical monomers via the helical oligomers and α‐helices to β‐sheets transition, as confirmed by transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and reversed‐phase high performance liquid chromatography. The computational results also suggest that the critical nucleus of aggregation corresponds to hexamers, consistent with a recent mass‐spectroscopy study of hIAPP8‐20 aggregation. hIAPP8‐20 oligomers smaller than hexamers are helical and unstable, while the α‐to‐β transition starts from the hexamers. Converted β‐sheet‐rich oligomers first form β‐barrel structures as intermediates before aggregating into cross‐β nanofibrils. This study uncovers a complete picture of hIAPP8‐20 peptide oligomerization, aggregation nucleation via conformational conversion, formation of β‐barrel intermediates, and assembly of cross‐β protofibrils, thereby shedding light on the aggregation of full‐length hIAPP, a hallmark of pancreatic beta‐cell degeneration.

Multidrug resistance of bacteria is a major challenge due to the wide‐spread use of antibiotics. While a range of strategies have been developed in recent years, suppression of bacterial activity and virulence via their network of extracellular amyloid has rarely been explored, especially with nanomaterials. Here, silver nanoparticles and nanoclusters (AgNPs and AgNCs) capped with cationic branched polyethylenimine polymer are synthesized, and their antimicrobial potentials are determined at concentrations safe to mammalian cells. Compared with the ultrasmall AgNCs, AgNPs entail stronger binding to suppress the fibrillization of FapC, a major protein constituent of the extracellular amyloid matrix ofPseudomonas aeruginosa. Both types of nanoparticles exhibit concentration‐dependent antibiofilm and antimicrobial properties againstP. aeruginosa. At concentrations of 1 × 10⁻⁶mor below, both the bactericidal activity of AgNCs and the antibiofilm capacity of AgNPs are associated with their structure‐mediated bio–nano interactions but not ion release. For AgNPs, specifically, their antibiofilm potency correlates with their capacity of FapC fibrillization inhibition, but not with their bactericidal activity. This study demonstrates the antimicrobial potential of safe nanotechnology through the novel route of amyloidosis inhibition.

Functional liquid metal nanoparticles (NPs), produced from eutectic alloys of gallium, promise new horizons in the fields of sensors, microfluidics, flexible electronics, catalysis, and biomedicine. Here, the development of a vapor cavity generating ultrasonic platform for nebulizing liquid metal within aqueous media for the one‐step production of stable and functional liquid metal NPs is shown. The size distribution of the NPs is fully characterized and it is demonstrated that various macro and small molecules can also be grafted onto these liquid metal NPs during the liquid‐based nebulization process. The cytotoxicity of the NPs grafted with different molecules is further explored. Moreover, it is shown that it is possible to control the thickness of the oxide layer on the produced NPs using electrochemistry that can be embedded within the platform. It is envisaged that this platform can be adapted as a cost‐effective and versatile device for the rapid production of functional liquid metal NPs for future liquid metal‐based optical, electronic, catalytic, and biomedical applications.