Single Molecule Force Spectroscopy of CNGA1

Single molecule force spectroscopy (SMFS) is known to be one of the most powerful tool to investigate the relation between structure and function in molecules and proteins. The possibility to work in aqueous conditions at a single molecular level opens up an extraordinary perspective to investigate rare events at a molecular level of biological systems. Over the past years Atomic Force Microscopy (AFM) based on SMFS has provided us information, that is either difficult or impossible to get from any other method. In spite of its advancements, SMFS has not been applied to many molecules of biological relevance for several reasons, such as problems with the biological samples, data analysis and other technical issues. Indeed, the development and improvement of SMFS is becoming is very important to study biological molecules and proteins in their natural environment

Magnetogenesis from Anisotropic Universe

The existence of large-scale anisotropy can not be ruled out by the cosmic microwave background (CMB) radiation. Over the years, several models have been proposed in the context of anisotropic inflation to account for CMB's cold spot and hemispheric asymmetry. However, any small-scale anisotropy, if exists during inflation, is not constrained due to its nonlinear evolution in the subsequent phase. This small-scale anisotropy during inflation can play a non-trivial role in giving rise to the cosmic magnetic field, which is the subject of our present study. Assuming a particular phenomenological form of an anisotropic inflationary universe, we have shown that it can generate a large-scale magnetic field at $1$-Mpc scale with a magnitude $\sim 4\times 10^{-20}~G$, within the observed bound. Because of the anisotropy, the conformal flatness property is lost, and the Maxwell field is generated even without explicit coupling. This immediately resolves the strong coupling problem in the standard magnetogenesis scenario. In addition, assuming very low conductivity during the reheating era, we can further observe the evolution of the electromagnetic field with the equation of state (EoS) $\omega_{eff}$ and its effects on the present-day magnetic field.Comment: 15 pages, 5 figures. Comments are welcom

Physical virology:From virus self-assembly to particle mechanics

Viruses are highly ordered supramolecular complexes that have evolved to propagate by hijacking the host cell's machinery. Although viruses are very diverse, spreading through cells of all kingdoms of life, they share common functions and properties. Next to the general interest in virology, fundamental viral mechanisms are of growing importance in other disciplines such as biomedicine and (bio)nanotechnology. However, in order to optimally make use of viruses and virus-like particles, for instance as vehicle for targeted drug delivery or as building blocks in electronics, it is essential to understand their basic chemical and physical properties and characteristics. In this context, the number of studies addressing the mechanisms governing viral properties and processes has recently grown drastically. This review summarizes a specific part of these scientific achievements, particularly addressing physical virology approaches aimed to understand the self-assembly of viruses and the mechanical properties of viral particles. Using a physicochemical perspective, we have focused on fundamental studies providing an overview of the molecular basis governing these key aspects of viral systems. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Structural Heterogeneity of CNGA1 Channels Revealed by Electrophysiology and Single-Molecule Force Spectroscopy

The determination at atomic resolution of the three-dimensional molecular structure of membrane proteins such as receptors and several ion channels has been a major breakthrough in structural biology. The molecular structure of several members of the superfamily of voltage-gated ionic channels such as K+ and Na+ is now available. However, despite several attempts, the molecular structure at atomic resolution of the full cyclic nucleotide-gated (CNG) ion channel, although a member of the same superfamily of voltage-gated ion channels, has not been obtained yet, neither by X-ray crystallography nor by electron cryomicroscopy (cryo-EM). It is possible that CNG channels have a high structural heterogeneity, making difficult crystallization and single-particle analysis. To address this issue, we have combined single-molecule force spectroscopy (SMFS) and electrophysiological experiments to characterize the structural heterogeneity of CNGA1 channels expressed in Xenopus laevis oocytes. The unfolding of the cytoplasmic domain had force peaks, occurring with a probability from 0.2 to 0.96. Force peaks during the unfolding of the transmembrane domain had a probability close to 1, but the distribution of the increase in contour length between two successive force peaks had multiple maxima differing by tens of nanometers. Concomitant electrophysiological experiments showed that the rundown in mutant channels S399C is highly variable and that the effect of thiol reagents when specific residues were mutated was consistent with a dynamic structural heterogeneity. These results show that CNGA1 channels have a wide spectrum of native conformations that are difficult to detect with X-ray crystallography and cryo-EM

Observable signals in a string inspired axion-dilaton background and Randall-Sundrum scenario

Rotation angle of the plane of polarization of the distant galactic radio waves has been estimated in a string inspired axion-dilaton background. It is found that the axion,dual to the field strength of the second rank antisymmetric massless Kalb-Ramond field in the string spectrum, produces a wavelength independent optical rotation which is much larger than that produced by the dilaton. Detection of such rotation has been reported in some recent cosmological experiments. The observed value has been compared with our estimated theoretical value following various cosmological constraints. The effects of warped extra dimensions in a braneworld scenario on such an optical rotation have been investigated.Comment: 17 Pages, Latex, article revised, To appear in Physical Review

Visualization of Single Molecules Building a Viral Capsid Protein Lattice through Stochastic Pathways

Direct visualization of pathways followed by single molecules while they spontaneously self-assemble into supramolecular biological machines may provide fundamental knowledge to guide molecular therapeutics and the bottom-up design of nanomaterials and nanodevices. Here, high-speed atomic force microscopy is used to visualize self-assembly of the bidimensional lattice of protein molecules that constitutes the framework of the mature human immunodeficiency virus capsid. By real-time imaging of the assembly reaction, individual transient intermediates and reaction pathways followed by single molecules could be revealed. As when assembling a jigsaw puzzle, the capsid protein lattice is randomly built. Lattice patches grow independently from separate nucleation events whereby individual molecules follow different paths. Protein subunits can be added individually, while others form oligomers before joining a lattice or are occasionally removed from the latter. Direct real-time imaging of supramolecular self-assembly has revealed a complex, chaotic process involving multiple routes followed by individual molecules that are inaccessible to bulk (averaging) techniques

New views on phototransduction from atomic force microscopy and single molecule force spectroscopy on native rods

By combining atomic force microscopy (AFM) imaging and single-molecule force spectroscopy (SMFS), we analyzed membrane proteins of the rod outer segments (OS). With this combined approach we were able to study the membrane proteins in their natural environment. In the plasma membrane we identified native cyclic nucleotide-gated (CNG) channels which are organized in single file strings. We also identified rhodopsin located both in the discs and in the plasma membrane. SMFS reveals strikingly different mechanical properties of rhodopsin unfolding in the two environments. Molecular dynamic simulations suggest that this difference is likely to be related to the higher hydrophobicity of the plasma membrane, due to the higher cholesterol concentration. This increases rhodopsin mechanical stability lowering the rate of transition towards its active form, hindering, in this manner, phototransduction

Visualization of single molecules building a viral capsid protein lattice through stochastic pathways

Direct visualization of pathways followed by single molecules while they spontaneously self-assemble into supramolecular biological machines may provide fundamental knowledge to guide molecular therapeutics and the bottom-up design of nanomaterials and nanodevices. Here, high-speed atomic force microscopy is used to visualize self-assembly of the bidimensional lattice of protein molecules that constitutes the framework of the mature human immunodeficiency virus capsid. By real-time imaging of the assembly reaction, individual transient intermediates and reaction pathways followed by single molecules could be revealed. As when assembling a jigsaw puzzle, the capsid protein lattice is randomly built. Lattice patches grow independently from separate nucleation events whereby individual molecules follow different paths. Protein subunits can be added individually, while others form oligomers before joining a lattice or are occasionally removed from the latter. Direct real-time imaging of supramolecular selfassembly has revealed a complex, chaotic process involving multiple routes followed by individual molecules that are inaccessible to bulk (averaging) technique

Characterization of Cyclic Nucleotide Gated Channels using Atomic Force Microscope

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