Biology helps to construct weighted scale free networks

In this work we study a simple evolutionary model of bipartite networks which its evolution is based on the duplication of nodes. Using analytical results along with numerical simulation of the model, we show that the above evolutionary model results in weighted scale free networks. Indeed we find that in the one mode picture we have weighted networks with scale free distributions for interesting quantities like the weights, the degrees and the weighted degrees of the nodes and the weights of the edges.Comment: 15 pages, 7 figures, Revte

Single-cell metabolomics by mass spectrometry: advances, challenges, and future applications

Cellular heterogeneity is a phenomenon that is often observed but poorly understood. Single-cell metabolomics can provide insights into the phenotypical variations between individual cells. Recent advances in microfluidics, micromanipulation, image analysis, and automation allowed for high-throughput isolation of single cells in a minimally disruptive manner as to not affect the cell metabolism. Coupled with new innovations in mass spectrometry-based analytical techniques, single cell metabolomics stands at the cusp of becoming an established field. In this review, some of the recent single cell isolation platforms that are especially suited for metabolomics will be highlighted, as well as the recent trends in mass spectrometry-based single cell platforms. Additionally, some of the limitations of single-cell metabolomics and its recent applications will be briefly discussed. (c) 2019 Elsevier B.V. All rights reserved.Analytical BioScience

A microfluidics-based screening tool to assess the impact of blood plasma factors on microvascular integrity

This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using a recently developed microvessel-on-a-chip platform featuring the human endothelium that is partly surrounded by the extracellular matrix. The system is high-throughput, which allows parallel analysis of organ-level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid plasma samples are mixed with inhibitors for recalcification of the plasma samples to avoid activation of the coagulation- or complement system. Moreover, the assay is validated by spiking vascular endothelial growth factor, histamine, or tumor necrosis factor alpha to recalcified plasma and confirms their modulation of microvessel barrier function at physiologically relevant concentrations. Finally, this study shows that perfusing the microvessels with recalcified plasma samples of coronavirus disease-2019 patients, with a confirmed proinflammatory profile, results in markedly increased leakage of the microvessels. The assay provides opportunities for diagnostic screening of inflammatory or endothelial disrupting plasma factors associated with endothelial dysfunction.Analytical BioScience

Organoids and organ chips in ophthalmology

Recent advances have driven the development of stem cell-derived, self-organizing, three-dimensional miniature organs, termed organoids, which mimic different eye tissues including the retina, cornea, and lens. Organoids and engineered microfluidic organ-on-chips (organ chips) are transformative technologies that show promise in simulating the architectural and functional complexity of native organs. Accordingly, they enable exploration of facets of human disease and development not accurately recapitulated by animal models. Together, these technologies will increase our understanding of the basic physiology of different eye structures, enable

Facile formation of highly mobile supported lipid bilayers on surface-quaternized pH-responsive polymer brushes

Poly(2-dimethylamino)ethyl methacrylate) (PDMA) brushes are grown from planar substrates via surface atom transfer radical polymerization (ATRP). Quaternization of these brushes is conducted using 1-iodooctadecane in n-hexane, which is a non-solvent for PDMA. Ellipsometry, AFM, and water contact angle measurements show that surface-confined quaternization occurs under these conditions, producing pH-responsive brushes that have a hydrophobic upper surface. Systematic variation of the 1-iodooctadecane concentration and reaction time enables the mean degree of surface quaternization to be optimized. Relatively low degrees of surface quaternization (ca. 10 mol % as judged by XPS) produce brushes that enable the formation of supported lipid bilayers, with the hydrophobic pendent octadecyl groups promoting in situ rupture of lipid vesicles. Control experiments confirm that quaternized PDMA brushes prepared in a good brush solvent (THF) produce non-pH-responsive brushes, presumably because the pendent octadecyl groups form micelle-like physical cross-links throughout the brush layer. Supported lipid bilayers (SLBs) can also be formed on the non-quaternized PDMA precursor brushes, but such structures proved to be unstable to small changes in pH. Thus, surface quaternization of PDMA brushes using 1-iodooctadecane in n-hexane provides the best protocol for the formation of robust SLBs. Fluorescence recovery after photobleaching (FRAP) studies of such SLBs indicate diffusion coefficients (2.8 ± 0.3 μm s–1) and mobile fractions (98 ± 2%) that are comparable to the literature data reported for SLBs prepared directly on planar glass substrates

Methods of probing the interactions between small molecules and disordered proteins

It is generally recognized that a large fraction of the human proteome is made up of proteins that remain disordered in their native states. Despite the fact that such proteins play key biological roles and are involved in many major human diseases, they still represent challenging targets for drug discovery. A major bottleneck for the identification of compounds capable of interacting with these proteins and modulating their disease-promoting behaviour is the development of effective techniques to probe such interactions. The difficulties in carrying out binding measurements have resulted in a poor understanding of the mechanisms underlying these interactions. In order to facilitate further methodological advances, here we review the most commonly used techniques to probe three types of interactions involving small molecules: (1) those that disrupt functional interactions between disordered proteins; (2) those that inhibit the aberrant aggregation of disordered proteins, and (3) those that lead to binding disordered proteins in their monomeric states. In discussing these techniques, we also point out directions for future developments.Gabriella T. Heller is supported by the Gates Cambridge Trust Scholarship. Francesco A. Aprile is supported by a Senior Research Fellowship award from the Alzheimer’s Society, UK (grant number 317, AS-SF-16-003)

Topology of internally constrained polymer chains

Linear chains with intra-chain contacts can adopt different topologies and allow transitions between them, but it remains unclear how this process can be controlled. This question is important to systems ranging from proteins to chromosomes, which can adopt different conformations that are key to their function and toxicity. Here, we investigate how the topological dynamics of a simple linear chain is affected by interactions with a binding partner, using Monte Carlo and Molecular Dynamics simulations. We show that two point contacts with a binding partner are sufficient to accelerate or decelerate the formation of particular topologies within linear chains. Computed ''folding-time landscapes" that detail the folding time within the topology space show that such contacts deform these landscapes and hence alter the occupation probability of topological states. The results provide a mechanism by which chain topologies can be controlled externally, which opens up the possibility of regulating topological dynamics and the formation of more complex topologies. The findings may have important implications for understanding the mechanism of chaperone action as well as genome architecture and evolution