Producing protein nanotubes by sacrificing nanofibres
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Intracellular assembly of supramolecular peptide nanostructures controlled by visible light
The complex dynamics of synthetic supramolecular systems in living cellular environments impede the correlation between the transient hierarchical species and their biological functions. Achieving this correlation demands a breakthrough that combines the precise control of supramolecular events at discrete time points via synthetic chemistry with their real-time visualization in native cells. In the present study, we reported two peptide sequences that undergo visible light-induced molecular and supramolecular transformations to form various assembly species in cells. In contrast to endogenous stimulus-responsive assembly, the proposed photochemistry enables full control over the photolysis reaction where the monomer generation and local concentration regulate the subsequent assembly kinetics. Phasor-fluorescence lifetime imaging traced the formation of various assembly states in cells associated with monomer activation and consumption, whereas correlative light-electron microscopy revealed the intracellular nanofibres formed. The temporally resolved assembly process shows that the emergence of cytotoxicity correlates with the accumulation of oligomers beyond the cellular efflux threshold.
Anionic lipids direct efficient microfluidic encapsulation of stable and functionally active proteins in lipid nanoparticles
Because proteins do not efficiently pass through the plasma membrane, protein therapeutics are limited to target ligands located at the cell surface or in serum. Lipid nanoparticles can facilitate delivery of polar molecules across a membrane. We hypothesized that because most proteins are amphoteric ionizable polycations, proteins would associate with anionic lipids, enabling microfluidic chip assembly of stable EP-LNPs (Encapsulated Proteins in Lipid NanoParticles). Here, by employing anionic lipids we were able to efficiently load proteins into EP-LNPs at protein:lipid w:w ratios of 1:20. Several proteins with diverse molecular weights and isoelectric points were encapsulated at efficiencies of 70 75%–90% and remained packaged for several months. Proteins packaged in EP-LNPs efficiently entered mammalian cells and fungal cells with cell walls. The proteins delivered intracellularly were functional. EP-LNPs technology should improve cellular delivery of medicinal antibodies, enzymes, peptide antimetabolites, and dominant negative proteins, opening new fields of protein therapeutics
Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men
Dietary protein restriction increases energy expenditure and enhances insulin sensitivity in mice. However, the effects of a eucaloric protein-restricted diet in healthy humans remain unexplored. Here, we show in lean, healthy men that a protein-restricted diet meeting the minimum protein requirements for 5 weeks necessitates an increase in energy intake to uphold body weight, regardless of whether proteins are replaced with fats or carbohydrates. Upon reverting to the customary higher protein intake in the following 5 weeks, energy requirements return to baseline levels, thus preventing weight gain. We also show that fasting plasma FGF21 levels increase during protein restriction. Proteomic analysis of human white adipose tissue and in FGF21-knockout mice reveal alterations in key components of the electron transport chain within white adipose tissue mitochondria. Notably, in male mice, these changes appear to be dependent on FGF21. In conclusion, we demonstrate that maintaining body weight during dietary protein restriction in healthy, lean men requires a higher energy intake, partially driven by FGF21-mediated mitochondrial adaptations in adipose tissue.
Flash Joule heating for synthesis, upcycling and remediation
Electric heating methods are being developed and used to electrify industrial applications and lower their carbon emissions. Direct Joule resistive heating is an energy-efficient electric heating technique that has been widely tested at the bench scale and could replace some energy-intensive and carbon-intensive processes. In this Review, we discuss the use of flash Joule heating (FJH) in processes that are traditionally energy-intensive or carbon-intensive. FJH uses pulse current discharge to rapidly heat materials directly to a desired temperature; it has high-temperature capabilities (>3,000 °C), fast heating and cooling rates (>102 °C s−1), short duration (milliseconds to seconds) and high energy efficiency (~100%). Carbon materials and metastable inorganic materials can be synthesized using FJH from virgin materials and waste feedstocks. FJH is also applied in resource recovery (such as from e-waste) and waste upcycling. An emerging application is in environmental remediation, where FJH can be used to rapidly degrade perfluoroalkyl and polyfluoroalkyl substances and to remove or immobilize heavy metals in soil and solid wastes. Life-cycle and technoeconomic analyses suggest that FJH can reduce energy consumption and carbon emissions and be cost-efficient compared with existing methods. Bringing FJH to industrially relevant scales requires further equipment and engineering development.
The comprehensive SARS-CoV-2 ‘hijackome’ knowledge base
The continuous evolution of SARS-CoV-2 has led to the emergence of several variants of concern (VOCs) that significantly affect global health. This study aims to investigate how these VOCs affect host cells at proteome level to better understand the mechanisms of disease. To achieve this, we first analyzed the (phospho)proteome changes of host cells infected with Alpha, Beta, Delta, and Omicron BA.1 and BA.5 variants over time frames extending from 1 to 36 h post infection. Our results revealed distinct temporal patterns of protein expression across the VOCs, with notable differences in the (phospho)proteome dynamics that suggest variant-specific adaptations. Specifically, we observed enhanced expression and activation of key components within crucial cellular pathways such as the RHO GTPase cycle, RNA splicing, and endoplasmic reticulum-associated degradation (ERAD)-related processes. We further utilized proximity biotinylation mass spectrometry (BioID-MS) to investigate how specific mutation of these VOCs influence viral–host protein interactions. Our comprehensive interactomics dataset uncovers distinct interaction profiles for each variant, illustrating how specific mutations can change viral protein functionality. Overall, our extensive analysis provides a detailed proteomic profile of host cells for each variant, offering valuable insights into how specific mutations may influence viral protein functionality and impact therapeutic target identification. These insights are crucial for the potential use and design of new antiviral substances, aiming to enhance the efficacy of treatments against evolving SARS-CoV-2 variants.
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