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Reaction network starting from monomer mixtures of Aβ40 and Aβ42. Interaction at the level of primary nucleation only accelerates Aβ40 fibril formation. Separate fibrils form as secondary nucleation and elongation are highly specific.

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The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein–protein interactions has increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats. Such consensus formats should become accepted in the field and be shown to lead to reproducible results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. Our study therefore builds the framework for establishing best practice guidelines to conduct cross-linking experiments, perform data analysis, and define reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results.

When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a "corona". This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in preclinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size-and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP. Recent years have witnessed an exceptional progress in research and applications in the field of nanoscience and nanotechnology 1. This emergent application of nanoparticles (NP) is revolutionizing several aspects of modern medicine due to NP features like longer circulation times, increased solubility, sustained delivery, protection from physical and chemical degradation and also control release of drugs 2-4. However, a few number of nano-approaches have been accepted for clinical use, while the majority of nanomaterials under clinical research have shown unsatisfactory results 5-8. In fact, one major obstacle to the successful clinical translation of new nanomedicines is the lack of an accurate understanding of their in vivo performance at systemic, tissue, and cellular levels 7. Once the nanomaterials interact with biological systems, proteins, lipids and other biomolecules, adsorb on their surfaces promoting the formation of the so-called "biocorona" 9-12. The formation of the biocorona is a dynamical process, driven by minimization of NP high surface free energy, in which different molecules of the biological fluid compete for the NP available surface 10,13. The biocorona is responsible for physical and chemical modifications on the nanomaterial, such as size, aggregation and surface properties, conferring it a biological identity different from the primary synthetic identity 14,15. Being the NP interface interacting with cells, the biocorona is thought to influence the NP circulation half-time 16 , biodistribution and uptake by cells 17,18 , and host immune response 19,20 , toxicity 21 and oxidative stress 22,23. The adsorption of proteins is influenced specifically by NP properties (size, hydrophobicity, c...