Giant capsids from lattice self-assembly of cyclodextrin complexes

Proteins can readily assemble into rigid, crystalline and functional structures such as viral capsids and bacterial compartments. Despite ongoing advances, it is still a fundamental challenge to design and synthesize protein-mimetic molecules to form crystalline structures. Here we report the lattice self-assembly of cyclodextrin complexes into a variety of capsidlike structures such as lamellae, helical tubes and hollow rhombic dodecahedra. The dodecahedral morphology has not hitherto been observed in self-assembly systems. The tubes can spontaneously encapsulate colloidal particles and liposomes. The dodecahedra and tubes are respectively comparable to and much larger than the largest known virus. In particular, the resemblance to protein assemblies is not limited to morphology but extends to structural rigidity and crystallinity-a well-defined, 2D rhombic lattice of molecular arrangement is strikingly universal for all the observed structures. We propose a simple design rule for the current lattice self-assembly, potentially opening doors for new protein-mimetic materials

Random, blocky and alternating ordering in supramolecular polymers of chemically bidisperse monomers

As a first step to understanding the role of molecular or chemical polydispersity in self-assembly, we put forward a coarse-grained model that describes the spontaneous formation of quasi-linear polymers in solutions containing two self-assembling species. Our theoretical framework is based on a two-component self-assembled Ising model in which the bidispersity is parameterized in terms of the strengths of the binding free energies that depend on the monomer species involved in the pairing interaction. Depending upon the relative values of the binding free energies involved, different morphologies of assemblies that include both components are formed, exhibiting paramagnetic-, ferromagnetic- or anti ferromagnetic-like order,i.e., random, blocky or alternating ordering of the two components in the assemblies. Analyzing the model for the case of ferromagnetic ordering, which is of most practical interest, we find that the transition from conditions of minimal assembly to those characterized by strong polymerization can be described by a critical concentration that depends on the concentration ratio of the two species. Interestingly, the distribution of monomers in the assemblies is different from that in the original distribution, i.e., the ratio of the concentrations of the two components put into the system. The monomers with a smaller binding free energy are more abundant in short assemblies and monomers with a larger binding affinity are more abundant in longer assemblies. Under certain conditions the two components congregate into separate supramolecular polymeric species and in that sense phase separate. We find strong deviations from the expected growth law for supramolecular polymers even for modest amounts of a second component, provided it is chemically sufficiently distinct from the main one.Comment: Submitted to Macromolecules, 6 figures. arXiv admin note: substantial text overlap with arXiv:1111.176

On the crystal lattice parameters of graphite-like phases of the B-C system

The structure of graphite-like BCx phases (x = 1, 1.5, 3, 4, 32) has been studied using conventional X-ray diffraction. The results have been obtained, which unambiguously point to turbostratic (one- dimensionally disordered) structure of all phases under study. The crystal lattice parameters, sizes of coherent scattering domains, and microstrain values have been defined, which have allowed us to find a correlation between the structure and stoichiometry of the phases synthesized at the same temperature

Single-molecule experiments in biological physics: methods and applications

I review single-molecule experiments (SME) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SME it is possible to: manipulate molecules one at a time and measure distributions describing molecular properties; characterize the kinetics of biomolecular reactions and; detect molecular intermediates. SME provide the additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SME it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level emphasizing the importance of SME to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SME from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers (MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation), proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SME to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond. Matt

Useful scars: Physics of the capsids of archaeal viruses

We propose a physical model for the capsids of tailed archaeal viruses as viscoelastic membranes under tension. The fluidity is generated by thermal motion of scarlike structures that are an intrinsic feature of the ground state of large particle arrays covering surfaces with nonzero Gauss curvature. The tension is generated by a combination of the osmotic pressure of the enclosed genome and an extension force generated by filamentous structure formation that drives the formation of the tails. In continuum theory, the capsid has the shape of a surface of constant mean curvature: an unduloid. Particle arrays covering unduloids are shown to exhibit pronounced subdiffusive and diffusive single-particle transport at temperatures that are well below the melting temperature of defect-free particle arrays on a surface with zero Gauss curvature

Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented)

Assertive community treatment for elderly people with severe mental illness

Background: Adults aged 65 and older with severe mental illnesses are a growing segment of the Dutch population. Some of them have a range of serious problems and are also difficult to engage. While assertive community treatment is a common model for treating difficult to engage severe mental illnesses patients, no special form of it is available for the elderly. A special assertive community treatment team for the elderly is developed in Rotterdam, the Netherlands and tested for its effectiveness.Methods: We will use a randomized controlled trial design to compare the effects of assertive community treatment for the elderly with those of care as usual. Primary outcome measures will be the number of dropouts, the number of patients engaged in care and patient's psychiatric symptoms, somatic symptoms, and social functioning. Secondary outcome measures are the number of unmet needs, the subjective quality of life and patients' satisfaction. Other secondary outcomes include the number of crisis contacts, rates of voluntary and involuntary admission, and length of stay. Inclusion criteria are aged 65 plus, the presence of a mental disorder, a lack of motivation for treatment and at least four suspected problems with functioning (addiction, somatic problems, daily living activities, housing etc.). If patients meet the inclusion criteria, they will be randomly allocated to either assertive community treatment for the elderly or care as usual. Trained assessors will use mainly observational instruments at the following time points: at baseline, after 9 and 18 months.Discussion: This study will help establish whether assertive community treatment for the elderly produces better results than care as usual in elderly people with severe mental illnesses who are difficult to engage. When assertive community treatment for the elderly proves valuable in these respects, it can be tested and implemented more widely, and mechanisms for its effects investigated

Task-Dependent Inhomogeneous Muscle Activities within the Bi-Articular Human Rectus Femoris Muscle

The motor nerve of the bi-articular rectus femoris muscle is generally split from the femoral nerve trunk into two sub-branches just before it reaches the distal and proximal regions of the muscle. In this study, we examined whether the regional difference in muscle activities exists within the human rectus femoris muscle during maximal voluntary isometric contractions of knee extension and hip flexion. Surface electromyographic signals were recorded from the distal, middle, and proximal regions. In addition, twitch responses were evoked by stimulating the femoral nerve with supramaximal intensity. The root mean square value of electromyographic amplitude during each voluntary task was normalized to the maximal compound muscle action potential amplitude (M-wave) for each region. The electromyographic amplitudes were significantly smaller during hip flexion than during knee extension task for all regions. There was no significant difference in the normalized electromyographic amplitude during knee extension among regions within the rectus femoris muscle, whereas those were significantly smaller in the distal than in the middle and proximal regions during hip flexion task. These results indicate that the bi-articular rectus femoris muscle is differentially controlled along the longitudinal direction and that in particular the distal region of the muscle cannot be fully activated during hip flexion

The influence of habitat structure on genetic differentiation in red fox populations in north-eastern Poland

The red fox (Vulpes vulpes) has the widest global distribution among terrestrial carnivore species, occupying most of the Northern Hemisphere in its native range. Because it carries diseases that can be transmitted to humans and domestic animals, it is important to gather information about their movements and dispersal in their natural habitat but it is difficult to do so at a broad scale with trapping and telemetry. In this study, we have described the genetic diversity and structure of red fox populations in six areas of north-eastern Poland, based on samples collected from 2002–2003. We tested 22 microsatellite loci isolated from the dog and the red fox genome to select a panel of nine polymorphic loci suitable for this study. Genetic differentiation between the six studied populations was low to moderate and analysis in Structure revealed a panmictic population in the region. Spatial autocorrelation among all individuals showed a pattern of decreasing relatedness with increasing distance and this was not significantly negative until 93 km, indicating a pattern of isolation-by-distance over a large area. However, there was no correlation between genetic distance and either Euclidean distance or least-cost path distance at the population level. There was a significant relationship between genetic distance and the proportion of large forests and water along the Euclidean distances. These types of habitats may influence dispersal paths taken by red foxes, which is useful information in terms of wildlife disease management