On the influence of bending energy on the assembly of spherical viral capsids.

The protective shell, or capsid, of many spherical viruses is formed via a self-assembly process whose underlying physical principles have not yet been fully elucidated. In this article, we analyze the role of elastic bending energy in the in vitro self-assembly of a spherical capsid in the limit where such energetic contribution dominates over compression stress. The model predicts that the capsid closes prematurely, and its final size is completely determined by a dimensionless constant fr, which is the ratio of the bending modulus to the line tension of the edge.

Assembly of tubes in the stretching-dominated limit.

Many biological and nanotechnological processes rely on the self-assembly of tubular structures. For this reason, theoretical models that offer insights into this process and ways to control its final outcome are essential. In this work, we study the conditions under which tubules are self-assembled spontaneously from free subunits in solution and explore the possible formation pathways using classical nucleation theory and an elastic model in the stretching-dominated regime.

Kinetic Description of Viral Capsid Self-Assembly Using Mesoscopic Non-Equilibrium Thermodynamics.

The self-assembly mechanisms of various complex biological structures, including viral capsids and carboxysomes, have been theoretically studied through numerous kinetic models. However, most of these models focus on the equilibrium aspects of a simplified kinetic description in terms of a single reaction coordinate, typically the number of proteins in a growing aggregate, which is often insufficient to describe the size and shape of the resulting structure. In this article, we use mesoscopic non-equilibrium thermodynamics (MNET) to derive the equations governing the non-equilibrium kinetics of viral capsid formation.

The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models.

Recent research has shown that mtDNA-deficient cancer cells (ρ cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1) mice markedly delayed tumor formation after grafting ρ cancer cells.

Theoretical Studies on Assembly, Physical Stability, and Dynamics of Viruses.

All matter must obey the general laws of physics and living matter is not an exception. Viruses have not only learnt how to cope with them but have managed to use them for their own survival. In this chapter, we will review some of the exciting physics that are behind viruses and discuss simple physical models that can shed some light on different aspects of the viral life cycle and viral properties.

Estimating metastable thermodynamic properties by isochoric extrapolation from stable states.

The description of metastable fluids, those in local but not global equilibrium, remains an important problem of thermodynamics, and it is crucial for many industrial applications and all first order phase transitions. One way to estimate their properties is by extrapolation from nearby stable states. This is often done isothermally, in terms of a virial expansion for gases or a Taylor expansion in density for liquids.

Collective motion of Nafion-based micromotors in water.

Ion exchange is one of the most interesting processes occurring at the interface between aqueous solutions and polymers, such as the well-known Nafion. If the exchanged ions have different diffusion coefficients, this interchange generates local electric fields which can be harnessed to drive fluid motion. In this work, we show how it is possible to design and fabricate self-propelling microswimmers based on Nafion, driven by ion-exchange, and fueled by innocuous salts.

Detection of pyrimidine-rich DNA sequences based on the formation of parallel and antiparallel triplex DNA and fluorescent silver nanoclusters.

In this work, the use of DNA-stabilized fluorescent silver nanoclusters for the detection of target pyrimidine-rich DNA sequences by formation of parallel and antiparallel triplex structures is studied by molecular fluorescence spectroscopy. In the case of parallel triplexes, the probe DNA fragments are Watson-Crick stabilized hairpins, and whereas in the case of antiparallel triplexes, the probe fragments are reverse-Hoogsteen clamps. In all cases, the formation of the triplex structures has been assessed by means of polyacrylamide gel electrophoresis, circular dichroism, and molecular fluorescence spectroscopies, as well as multivariate data analysis methods.

Inferring assembly-curving trends of bacterial micro-compartment shell hexamers from crystal structure arrangements.

Bacterial microcompartments (BMC) are complex macromolecular assemblies that participate in varied chemical processes in about one fourth of bacterial species. BMC-encapsulated enzymatic activities are segregated from other cell contents by means of semipermeable shells, justifying why BMC are viewed as prototype nano-reactors for biotechnological applications. Herein, we undertook a comparative study of bending propensities of BMC hexamers (BMC-H), the most abundant shell constituents.

Free energy of critical droplets-from the binodal to the spinodal.

Arguably, the main challenge of nucleation theory is to accurately evaluate the work of formation of a critical embryo in the new phase, which governs the nucleation rate. In Classical Nucleation Theory (CNT), this work of formation is estimated using the capillarity approximation, which relies on the value of the planar surface tension. This approximation has been blamed for the large discrepancies between predictions from CNT and experiments.

Ablation of Influences Corticosterone Levels and Anxiety-like Behavior in Mice.

Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid concentration is linked to generalized anxiety, and there are knowledge gaps regarding its regulation.

Comprehensive Transcriptional Profiling and Mouse Phenotyping Reveals Dispensable Role for Adipose Tissue Selective Long Noncoding RNA .

Cold and nutrient-activated brown adipose tissue (BAT) is capable of increasing systemic energy expenditure via the uncoupled respiration and secretion of endocrine factors, thereby protecting mice against diet-induced obesity and improving insulin response and glucose tolerance in men. Long non-coding RNAs (lncRNAs) have recently been identified as fine-tuning regulators of cellular function. While certain lncRNAs have been functionally characterised in adipose tissue, their overall contribution in the activation of BAT remains elusive.

From radial to unidirectional water pumping in zeta-potential modulated Nafion nanostructures.

Chemically propelled micropumps are promising wireless systems to autonomously drive fluid flows for many applications. However, many of these systems are activated by nocuous chemical fuels, cannot operate at high salt concentrations, or have difficulty for controlling flow directionality. In this work we report on a self-driven polymer micropump fueled by salt which can trigger both radial and unidirectional fluid flows.

Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice.

Type 2 diabetes mellitus represents a major health problem with increasing prevalence worldwide. Limited efficacy of current therapies has prompted a search for novel therapeutic options. Here we show that treatment of pre-diabetic mice with mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, improves glucose tolerance and reduces body weight with most pronounced reduction of visceral adipose tissue due to reduced food intake, suppressed adipogenesis and elimination of senescent cells.

Bacteriophage PRD1 as a nanoscaffold for drug loading.

Viruses are very attractive biomaterials owing to their capability as nanocarriers of genetic material. Efforts have been made to functionalize self-assembling viral protein capsids on their exterior or interior to selectively take up different payloads. PRD1 is a double-stranded DNA bacteriophage comprising an icosahedral protein outer capsid and an inner lipidic vesicle.

Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis.

The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance.

Shape selection and mis-assembly in viral capsid formation by elastic frustration.

The successful assembly of a closed protein shell (or capsid) is a key step in the replication of viruses and in the production of artificial viral cages for bio/nanotechnological applications. During self-assembly, the favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated due to the curvature of the capsid. As a result, incomplete structures such as open caps, cylindrical or ribbon-shaped shells may emerge, preventing the successful replication of viruses.

Electrophoretic origin of long-range repulsion of colloids near water/Nafion interfaces.

One of the most striking properties of Nafion is the formation of a long-range solute exclusion zone (EZ) in contact with water. The mechanism of formation of this EZ has been the subject of a controversial and long-standing debate. Previous studies by Schurr et al.

Quantifying Human Engagement into Playful Activities.

Engaging in playful activities, such as playing a musical instrument, learning a language, or performing sports, is a fundamental aspect of human life. We present a quantitative empirical analysis of the engagement dynamics into playful activities. We do so by analyzing the behavior of millions of players of casual video games and discover a scaling law governing the engagement dynamics.

Curvature Corrections Remove the Inconsistencies of Binary Classical Nucleation Theory.

The study of nucleation in fluid mixtures exposes challenges beyond those of pure systems. A striking example is homogeneous condensation in highly surface-active water-alcohol mixtures, where classical nucleation theory yields an unphysical, negative number of water molecules in the critical embryo. This flaw has rendered multicomponent nucleation theory useless for many industrial and scientific applications.

Adenovirus major core protein condenses DNA in clusters and bundles, modulating genome release and capsid internal pressure.

Some viruses package dsDNA together with large amounts of positively charged proteins, thought to help condense the genome inside the capsid with no evidence. Further, this role is not clear because these viruses have typically lower packing fractions than viruses encapsidating naked dsDNA. In addition, it has recently been shown that the major adenovirus condensing protein (polypeptide VII) is dispensable for genome encapsidation.

Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus.

The functions performed by the concentric shells of multilayered dsRNA viruses require specific protein interactions that can be directly explored through their mechanical properties. We studied the stiffness, breaking force, critical strain and mechanical fatigue of individual Triple, Double and Single layered rotavirus (RV) particles. Our results, in combination with Finite Element simulations, demonstrate that the mechanics of the external layer provides the resistance needed to counteract the stringent conditions of extracellular media.

Unraveling the Operational Mechanisms of Chemically Propelled Motors with Micropumps.

The development of effective autonomous micro- and nanomotors relies on controlling fluid motion at interfaces. One of the main challenges in the engineering of such artificial machines is the quest for efficient mechanisms to power them without using external driving forces. In the past decade, there has been an important increase of man-made micro- and nanomotors fueled by self-generated physicochemical gradients.

The RNA-Binding Protein of a Double-Stranded RNA Virus Acts like a Scaffold Protein.

Infectious bursal disease virus (IBDV), a nonenveloped, double-stranded RNA (dsRNA) virus with a T=13 icosahedral capsid, has a virion assembly strategy that initiates with a precursor particle based on an internal scaffold shell similar to that of tailed double-stranded DNA (dsDNA) viruses. In IBDV-infected cells, the assembly pathway results mainly in mature virions that package four dsRNA segments, although minor viral populations ranging from zero to three dsRNA segments also form. We used cryo-electron microscopy (cryo-EM), cryo-electron tomography, and atomic force microscopy to characterize these IBDV populations.

Viral nanomechanics with a virtual atomic force microscope.

One of the most important components of a virus is the protein shell or capsid that encloses its genetic material. The main role of the capsid is to protect the viral genome against external aggressions, facilitating its safe and efficient encapsulation and delivery. As a consequence, viral capsids have developed astonishing mechanical properties that are crucial for viral function.