06 Feb 2020-bioRxiv (Cold Spring Harbor Laboratory)-
TL;DR: It is highlighted that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces, and the weakly interacting proteins in the SC are revealed as modulators of nanoparticle-cell association, in spite of their short residence time.
Abstract: The current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of analytical separation methods. Here, we identified a set of specific corona proteins with weak interactions at silica and polystyrene nanoparticles by using an in situ click-chemistry reaction. We show that these SC proteins are present also in the HC, but are specifically enriched after the capture, suggesting that the main distinction between HC and SC is the differential binding strength of the same proteins. Interestingly, the weakly interacting proteins in the SC are revealed as modulators of nanoparticle-cell association, in spite of their short residence time. We therefore highlight that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces.
TL;DR: The roadblocks that are still hindering the effective application of informatics and predictive computational nanotoxicology methods from providing more effective guidance to nanomaterials regulatory agencies and safe-by-design rationale for industry are discussed.
Abstract: The rapid rise of nanotechnology has resulted in a parallel rise in the number of products containing nanomaterials. The unusual properties that nano forms of materials exhibit relative to the bulk has driven intense research interest and relatively rapid adoption by industry. Regulatory agencies are charged with protecting workers, the public, and the environment from any adverse effects of nanomaterials that may also arise because of these novel physical and chemical properties. They need data and models that allow them to flag nanomaterials that may be of concern, while balancing potential stifling of commercial innovation. Roadmaps for the future of safe nanotechnology were defined more than a decade ago, but many roadblocks identified in these studies remain. Here, we discuss the roadblocks that are still hindering the effective application of informatics and predictive computational nanotoxicology methods from providing more effective guidance to nanomaterials regulatory agencies and safe-by-design rationale for industry. We describe how developments in high throughput synthesis, characterization, and biological assessment of nanomaterials will overcome many of these roadblocks, allowing a clearly defined roadmap for computational design of effective but safe-by-design nanomaterials to be realized.
Abstract: Although an established drug delivery platform, liposomes have not fulfilled their true potential. In the body, interactions of liposomes are mediated by the layer of plasma proteins adsorbed on the surface, the protein corona. The review aims to collect the data of the last decade on liposome protein corona, tracing the path from interactions of individual proteins to the effects mediated by the protein corona in vivo. It offers a classification of the approaches to exploitation of the protein corona—rather than elimination thereof—based on the bilayer composition–corona composition–molecular interactions–biological performance framework. The multitude of factors that affect each level of this relationship urge to the widest implementation of bioinformatics tools to predict the most effective liposome compositions relying on the data on protein corona. Supplementing the picture with new pieces of accurately reported experimental data will contribute to the accuracy and efficiency of the predictions. Statement of significance The review focuses on liposomes as an established nanomedicine platform and analyzes the available data on how the protein corona formed on liposome surface in biological fluids affects performance of the liposomes. The review offers a rigorous account of existing literature and critical analysis of methodology currently applied to the assessment of liposome–plasma protein interactions. It introduces a classification of the approaches to exploitation of the protein corona and tailoring liposome carriers to advance the field of nanoparticulate drug delivery systems for the benefit of patients.
TL;DR: FactoMineR an R package dedicated to multivariate data analysis with the possibility to take into account different types of variables (quantitative or categorical), different kinds of structure on the data, and finally supplementary information (supplementary individuals and variables).
Abstract: In this article, we present FactoMineR an R package dedicated to multivariate data analysis. The main features of this package is the possibility to take into account different types of variables (quantitative or categorical), different types of structure on the data (a partition on the variables, a hierarchy on the variables, a partition on the individuals) and finally supplementary information (supplementary individuals and variables). Moreover, the dimensions issued from the different exploratory data analyses can be automatically described by quantitative and/or categorical variables. Numerous graphics are also available with various options. Finally, a graphical user interface is implemented within the Rcmdr environment in order to propose an user friendly package.
TL;DR: The ExPASy (the Expert Protein Analysis System) World Wide Web server, provided as a service to the life science community by a multidisciplinary team at the Swiss Institute of Bioinformatics, provides access to a variety of databases and analytical tools dedicated to proteins and proteomics.
Abstract: The ExPASy (the Expert Protein Analysis System) World Wide Web server (http://www.expasy.org), is provided as a service to the life science community by a multidisciplinary team at the Swiss Institute of Bioinformatics (SIB). It provides access to a variety of databases and analytical tools dedicated to proteins and proteomics. ExPASy databases include SWISS-PROT and TrEMBL, SWISS-2DPAGE, PROSITE, ENZYME and the SWISS-MODEL repository. Analysis tools are available for specific tasks relevant to proteomics, similarity searches, pattern and profile searches, post-translational modification prediction, topology prediction, primary, secondary and tertiary structure analysis and sequence alignment. These databases and tools are tightly interlinked: a special emphasis is placed on integration of database entries with related resources developed at the SIB and elsewhere, and the proteomics tools have been designed to read the annotations in SWISS-PROT in order to enhance their predictions. ExPASy started to operate in 1993, as the first WWW server in the field of life sciences. In addition to the main site in Switzerland, seven mirror sites in different continents currently serve the user community.
TL;DR: Fuzzy Databases: Principles and Applications is comprehensive covering all of the major approaches and models of fuzzy databases that have been developed including coverage of commercial/industrial systems and applications.
Abstract: From the Publisher:
This volume presents the results of approximately 15 years of work from researchers around the world on the use of fuzzy set theory to represent imprecision in databases. The maturity of the research in the discipline and the recent developments in commercial/industrial fuzzy databases provided an opportunity to produce this survey. Fuzzy Databases: Principles and Applications is self-contained providing background material on fuzzy sets and database theory. It is comprehensive covering all of the major approaches and models of fuzzy databases that have been developed including coverage of commercial/industrial systems and applications. Background and introductory material are provided in the first two chapters. The major approaches in fuzzy databases comprise the second part of the volume. This includes the use of similarity and proximity measures as the fuzzy techniques used to extend the relational data modeling and the use of possibility theory approaches in the relational model. Coverage includes extensions to the data model, querying approaches, functional dependencies and other topics including implementation issues, information measures, database security, alternative fuzzy data models, the IFO model, and the network data models. A number of object-oriented extensions are also discussed. The use of fuzzy data modeling in geographical information systems (GIS) and use of rough sets in rough and fuzzy rough relational data models are presented. Major emphasis has been given to applications and commercialization of fuzzy databases. Several specific industrial/commercial products and applications are described. These include approaches to developing fuzzy front-end systems and special-purpose systems incorporating fuzziness.
TL;DR: The rates of protein association and dissociation are determined using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein–nanoparticle mixtures, and this method is developed into a systematic methodology to isolate nanoparticle-associated proteins.
Abstract: Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.
TL;DR: The basic concept of the nanoparticle corona is reviewed and its structure and composition is highlighted, and how the properties of the corona may be linked to its biological impacts are highlighted.
Abstract: The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.