Silk Protein Solution : A Natural Example of Sticky Reptation

Silk is one of the most intriguing examples of biomolecular self-assembly, yet little is understood of molecular mechanisms behind the flow behavior generating these complex high-performance fibers. This work applies the polymer physics of entangled solution rheology to present a first microphysical understanding of silk in the linear viscoelastic regime. We show that silk solutions can be approximated as reptating polymers with "sticky" calcium bridges whose strength can be controlled through the potassium concentration. This approach provides a new window into critical microstructural parameters, in particular identifying the mechanism by which potassium and calcium ions are recruited as a powerful viscosity control in silk. Our model constitutes a viable starting point to understand not only the "flow-induced self-assembly" of silk fibers but also a broader range of phenomena in the emergent field of material-focused synthetic biology

Molecular Dynamics Simulation of Dextran Extension by Constant Force in Single Molecule AFM

AbstractThe extension of 1–6 polysaccharides has been studied in a series of recent single molecule AFM experiments. For dextran, a key finding was the existence of a plateau in the force-extension curve at forces between 700 and 1000pN. We studied the extension of the dextran 10-mer under constant force using atomistic simulation with various force fields. All the force fields reproduce the experimental plateau on the force-extension curve. With AMBER94 and AMBER-GLYCAM04 force fields the plateau can be explained by a transition of the glucopyranose rings in the dextran monomers from the chair (4C1) to the inverted chair (1C4) conformation while other processes occur at smaller (rotation around C5-C6 bond) or higher (chairs to boat transitions) forces. The CHARMM force field provides a different picture which associates the occurrence of the plateau to chair-boat transitions of the glucopyranose rings

Ligand-regulated oligomerisation of allosterically interacting proteins

The binding of ligands to distinct sites at proteins or at protein clusters is often cooperative or anti-cooperative due to allosteric signalling between those sites. The allostery is usually attributed to a configurational change of the proteins from a relaxed to a configurationally different tense state. Alternatively, as originally proposed by Cooper and Dryden, a tense state may be achieved by merely restricting the thermal vibrations of the protein around its mean configuration. In this work, we provide theoretical tools to investigate fluctuation allostery using cooling and titration experiments in which ligands regulate dimerisation, or ring or chain formation. We discuss in detail how ligands may regulate the supramolecular (co)polymerisation of liganded and unliganded proteins

Magnifying Grains of Sand, Seeds, and Blades of Grass: Optical Effects in Robert Grosseteste’s De iride (On the Rainbow) (circa 1228–1230)

In his treatise On the Rainbow (De iride), composed nearly four hundred years before the first known telescope, the English polymath Robert Grosseteste identified three striking optical effects: distant objects can be rendered close by; close-by large objects can be rendered small; and distant small objects can be rendered large. In the context of the history of optics, the first effect is especially striking. Grosseteste did not give details of the mechanisms underlying these effects but did mention the passage of rays through refraction in “diaphanous” or transparent bodies. While making no final claim that Grosseteste himself necessarily knew of or used lenses, this essay examines the coherence between the three optical effects described in Grosseteste’s treatise and two candidate proposals for the deployment of a single convex lens. A convex lens, deployed in different ways, is shown to produce all three of Grosseteste’s optical effects, in a manner strikingly aligned with the language that he uses to distinguish changes in the location and size of objects. The implications of this coherence for interpretations of On the Rainbow are discussed throughout the essay

Controlled Synthesis, Characterization, and Flow Properties of Ethylene–Diene Copolymers

The flow response of branched entangled resins is dominated by the branching topology of the constituent molecules, a property that is not directly accessible using experimental analytical tools for industrially relevant complex resins. In this paper, the controlled terpolymerization of ethylene, 1,9-decadiene, and either hexene or octene in a continuous stirred tank reactor with a metallocene catalyst, is reported. The synthesized samples are characterized extensively with various analytical tools and their rheological properties are measured with small amplitude oscillatory shear and start-up uniaxial extension experiments. A model is developed for the polymerization process with the mass balance during synthesis providing strong constraints on the rate constants. In silico ensembles of molecules, generated via Monte Carlo sampling, are used to reproduce the experimental results. The computer model allows us to infer the detailed branching structure of the molecules and to predict the optimum range of reactor conditions for this synthesis

Substrate-Modulated Thermal Fluctuations Affect Long-Range Allosteric Signaling in Protein Homodimers: Exemplified in CAP

The role of conformational dynamics in allosteric signaling of proteins is increasingly recognized as an important and subtle aspect of this ubiquitous phenomenon. Cooperative binding is commonly observed in proteins with twofold symmetry that bind two identical ligands. We construct a coarse-grained model of an allosteric coupled dimer and show how the signal can be propagated between the distant binding sites via change in slow global vibrational modes alone. We demonstrate that modulation on substrate binding of as few as 5–10 slow modes can give rise to cooperativity observed in biological systems and that the type of cooperativity is given by change of interaction between the two monomers upon ligand binding. To illustrate the application of the model, we apply it to a challenging test case: the catabolite activator protein (CAP). CAP displays negative cooperativity upon association with two identical ligands. The conformation of CAP is not affected by the binding, but its vibrational spectrum undergoes a strong modification. Intriguingly, the first binding enhances thermal fluctuations, yet the second quenches them. We show that this counterintuitive behavior is, in fact, necessary for an optimal anticooperative system, and captured within a well-defined region of the model's parameter space. From analyzing the experimental results, we conclude that fast local modes take an active part in the allostery of CAP, coupled to the more-global slow modes. By including them into the model, we elucidate the role of the modes on different timescales. We conclude that such dynamic control of allostery in homodimers may be a general phenomenon and that our model framework can be used for extended interpretation of thermodynamic parameters in other systems

Emerging applications for models of molecular rheology

Our understanding of the rich and complex motion of macromolecules has developed rapidly in recent years, particularly in the entangled regime. In this paper we highlight examples of research that has exploited our detailed picture of macromolecular motion. These studies encompass a broad range of areas in polymer physics, including neutron scattering under strong flow, tear properties of oriented polymers, flow-induced crystallisation and single molecule rheology of biopolymers. In each case molecular modelling plays a key role in understanding the observed phenomena

Listening Between the Lines: Medieval and Modern Science

In this article the investigators of the Ordered Universe project will reflect on how a diverse range of disciplinary perspectives essential for effective research into medieval science have been identified, acknowledged and absorbed into a genuinely interdisciplinary methodology. The project operates with a radical interdisciplinary composition bridging science and humanities in particular. How to translate what might be termed current academic practices and expectations between disciplines and between colleagues is a key issue. The article explores the practices of collaborative discussion, collaborative reading and collaborative writing. Central to these issues is the notion of the “atmosphere of enquiry”: getting the best from disciplinary perspectives, respecting expertise and having the right to challenge disciplinary boundaries are integral elements within the process. Finally the experience of this project is set in the context of the wider discussion of what interdisciplinary research means. We discuss how the methods of the Ordered Universe might be used, by imitation or by analogy. This article is published as part of a collection on interdisciplinarity