Order/Disorder in Protein and Peptide-Based Biomaterials

Nature utilizes both order and disorder (or controlled disorder) to achieve exceptional materials properties and functions, while synthetic supramolecular materials mostly exploit just supramolecular order, thus limiting the structural diversity, responsiveness and consequent adaptive functions that can be accessed. Herein, we review the emerging field of supramolecular biomaterials where disorder and order deliberately co-exist, and can be dynamically regulated by considering both entropic and enthalpic factors in design. We focus on sequence-structure relationships that govern the (cooperative) assembly pathways of protein and peptide building blocks in these materials. Increasingly, there is an interest in introducing dynamic features in protein and peptide-based structures, such as the remarkable thermo-responsiveness and exceptional mechanical properties of elastin materials. Simultaneously, advances in the field of intrinsically disordered proteins (IDPs) give new insights about their involvement in intracellular liquid-liquid phase separation and formation of disordered, dynamic coacervate structures. These have inspired efforts to design biomaterials with similar dynamic properties. These hybrid ordered/disordered materials employ a combination of intramolecular and supramolecular order/disorder features for construction of assemblies that are dynamically reconfigurable. The assembly of these dynamic structures is mainly entropy-driven, relying on electrostatic and hydrophobic interactions and is mediated in part through the adopted (unstructured) protein conformation or by introducing an oppositely charged guest for peptide building blocks. Examples include design of protein building blocks composed of disordered repeat sequences of elastin-like polypeptides in combination with ordered regions that adopt a secondary structure, the co-assembly of proteins with peptide amphiphiles to achieve reconfigurable, yet highly stable membranes or tyrosine-containing tripeptides with sequence-controlled order/disorder that upon enzymatic oxidation give rise to melanin-like polymeric pigments with customizable properties. The resulting hybrid materials with controlled disorder can be metastable, and sensitive to various external stimuli giving rise to insights that are especially attractive for the design of responsive and adaptive materials.     

Book reviews

Seasonality and seasons of Estonian landscapes are analysed using selected natural and social indicators of urban and rural landscapes. Seasonality has a great influence on the ecological and visual features of landscapes; seasonal variability is especially great in temperate climate zones where relatively cold winters alternate with warm summers. The indicators that are suitable for describing the seasonality of landscapes are natural parameters such as air temperature, radiation regime, climatic seasons and snow cover, and social parameters of birthdays, alcohol consumption and state budget allocations. Because of the great seasonal differences in natural and socio-economic conditions, the differences between urban and rural landscapes having different seasonal rhythms are focused upon. One of the main differences is the change in lifestyle which is detected in the change in the seasonal variability of births. Seasonal differences between urban and rural landscapes are also confirmed by parameters of changing climate and some social indicators. The developing information society creates new jobs and a lifestyle that has its own seasonal rhythm. Periods of active work and social activity accumulate towards the deadlines preceding the Christmas and the summer period of vacations. A project-oriented information society has more flexibility to enjoy nature in rural landscapes during different seasons.     

Reversible acetonitrile-induced inactivation/activation of thermolysin

Thermolysin is catalytically inactive in mixtures of 10-15 % acetonitrile in aqueous buffer. Unexpectedly, dilution of the inactive enzyme with acetonitrile leads to complete recovery of the catalytic activity in a similar way to dilution with aqueous buffer. Circular dichroism and fluorescence studies of thermolysin in the same solvent mixtures reveal discontinuous changes in the overall secondary and tertiary protein structure that correlate well with the reversible differences in catalytic activity. The spectra on either side of the minimum activity point are different from each other, a fact indicating that the enzyme may be able to access two active conformations which are thermodynamically stable in different solvent environments.     

Virus Matryoshka: A Bacteriophage Particle—Guided Molecular Assembly Approach to a Monodisperse Model of the Immature Human Immunodeficiency Virus

Immature human immunodeficiency virus type 1 (HIV‐1) is approximately spherical, but is constructed from a hexagonal lattice of the Gag protein. As a hexagonal lattice is necessarily flat, the local symmetry cannot be maintained throughout the structure. This geometrical frustration presumably results in bending stress. In natural particles, the stress is relieved by incorporation of packing defects, but the magnitude of this stress and its significance for the particles is not known. In order to control this stress, we have now assembled the Gag protein on a quasi‐spherical template derived from bacteriophage P22. This template is monodisperse in size and electron‐transparent, enabling the use of cryo‐electron microscopy in structural studies. These templated assemblies are far less polydisperse than any previously described virus‐like particles (and, while constructed according to the same lattice as natural particles, contain almost no packing defects). This system gives us the ability to study the relationship between packing defects, curvature and elastic energy, and thermodynamic stability. As Gag is bound to the P22 template by single‐stranded DNA, treatment of the particles with DNase enabled us to determine the intrinsic radius of curvature of a Gag lattice, unconstrained by DNA or a template. We found that this intrinsic radius is far larger than that of a virion or P22‐templated particle. We conclude that Gag is under elastic strain in a particle; this has important implications for the kinetics of shell growth, the stability of the shell, and the type of defects it will assume as it grows.     

The optimal level of fuzz: case studies in a methodology for psychological research

Cognitive science research is hard to conduct, because researchers must take phenomena from the world and turn them into laboratory tasks for which a reasonable level of experimental control can be achieved. Consequently, research necessarily makes tradeoffs between internal validity (experimental control) and external validity (the degree to which a task represents behaviour outside of the lab). Researchers are thus seeking the best possible trade-off between these constraints, which we refer to as the optimal level of fuzz. We present two principles for finding the optimal level of fuzz, in research, and then illustrate these principles using research from motivation, individual differences and cognitive neuroscience.