arXiv subjects

Roya Zandi

Publications and source records attributed to Roya Zandi.

At least 37 records · Page 2Linked to original sources

arXiv2019

Elasticity in Curved Topographies: Exact Theories and Linear Approximations

Almost all available results in elasticity on curved topographies are obtained within either a small curvature expansion or an empirical covariant generalization that accounts for screening between Gaussian curvature and disclinations. In this paper, we present a formulation of elasticity theory in curved geometries that unifies its underlying geometric and topological content with the theory of defects. The two different linear approximations widely used in the literature are shown to arise as systematic expansions in reference and actual space. Taking the concrete example of a 2D crystal, with and without a central disclination, constrained on a spherical cap, we compare the exact results with different approximations and evaluate their range of validity. We conclude with some general discussion about the universality of non-linear elasticity.

cond-mat.soft↗

arXiv2018

The equilibrium structure of self-assembled protein nano-cages

Understanding how highly symmetric, robust, monodisperse protein cages self-assemble can have major applications in various areas of bio-nanotechnology, such as drug delivery, biomedical imaging and gene therapy. We develop a model to investigate the assembly of protein subunits into the structures with different size and symmetry. Using Monte Carlo simulation, we obtain the global minimum energy structures. Our results suggest that the physical properties of building blocks including the spontaneous curvature, flexibility and bending rigidity of coat proteins are sufficient to predict the size of the assembly products and that the symmetry and shape selectivity of nano-cages can be explained, at least in part, on a thermodynamic basis. The polymorphism of nano-cages observed in vitro assembly experiments are also discussed.

cond-mat.soft↗

arXiv2018

Why large icosahedral viruses need scaffolding proteins: The interplay of Gaussian curvature and disclination interactions

While small single stranded viral shells encapsidate their genome spontaneously, many large viruses, such as the Herpes virus or Infectious Bursal Disease Virus (IBDV), typically require a template, consisting of either scaffolding proteins or inner core. Despite the proliferation of large viruses in nature, the mechanisms by which hundreds or thousands of proteins assemble to form structures with icosahedral order (IO) is completely unknown. Using continuum elasticity theory, we study the growth of large viral shells (capsids) and show that a non-specific template not only selects the radius of the capsid, but leads to the error-free assembly of protein subunits into capsids with universal IO. We prove that as a spherical cap grows, there is a deep potential well at the locations of disclinations that later in the assembly process will become the vertices of an icosahedron. Furthermore, we introduce a minimal model and simulate the assembly of viral shell around a template under non-equilibrium conditions and find a perfect match between the results of continuum elasticity theory and the numerical simulations. Besides explaining available experimental results, we provide a number of new predictions. Implications for other problems in spherical crystals are also discussed.

physics.bio-ph↗

arXiv2018

The effect of RNA stiffness on the self-assembly of virus particles

Under many in vitro conditions, some small viruses spontaneously encapsidate a single stranded (ss) RNA into a protein shell called the capsid. While viral RNAs are found to be compact and highly branched because of long distance base-pairing between nucleotides, recent experiments reveal that in a head-to-head competition between a ssRNA with no secondary or higher order structure and a viral RNA, the capsid proteins preferentially encapsulate the linear polymer! In this paper, we study the impact of genome stiffness on the encapsidation free energy of the complex of RNA and capsid proteins. We show that an increase in effective chain stiffness because of base-pairing could be the reason why under certain conditions linear chains have an advantage over branched chains when it comes to encapsidation efficiency. While branching makes the genome more compact, RNA base-pairing increases the effective Kuhn length of the RNA molecule, which could result in an increase of the free energy of RNA confinement, that is, the work required to encapsidate RNA, and thus less efficient packaging.

physics.bio-ph↗

arXiv2017

Self Consistent Field Theory of Virus Assembly

The Ground State Dominance Approximation(GSDA) has been extensively used to study the assembly of viral shells. In this work we employ the self-consistent field theory (SCFT) to investigate the adsorption of RNA onto positively charged spherical viral shells and examine the conditions when GSDA does not apply and SCFT has to be used to obtain a reliable solution. We find that there are two regimes in which GSDA does work. First, when the genomic RNA length is long enough compared to the capsid radius, and second, when the interaction between the genome and capsid is so strong that the genome is basically localized next to the wall. We find that for the case in which RNA is more or less distributed uniformly in the shell, regardless of the length of RNA, GSDA is not a good approximation. We observe that as the polymer-shell interaction becomes stronger, the energy gap between the ground state and first excited state increases and thus GSDA becomes a better approximation. We also present our results corresponding to the genome persistence length obtained through the tangent-tangent correlation length and show that it is zero in case of GSDA but is equal to the inverse of the energy gap when using SCFT.

physics.bio-ph↗

arXiv2017

RNA Base Pairing Determines the Conformations of RNA Inside Spherical Viruses

Many simple RNA viruses enclose their genetic material by a protein shell called the capsid. While the capsid structures are well characterized for most viruses, the structure of RNA inside the shells and the factors contributing to it remain poorly understood. We study the impact of base pairing on the conformations of RNA and find that it undergoes a swollen coil to globule continuous transition as a function of the strength of the pairing interaction. We also observe a first order transition and kink profile as a function of RNA length. All these transitions could explain the different RNA profiles observed inside viral shells.

physics.bio-ph↗

arXiv2017

Impact of a non-uniform charge distribution on virus assembly

Many spherical viruses encapsulate their genome in protein shells with icosahedral symmetry. This process is spontaneous and driven by electrostatic interactions between positive domains on the virus coat proteins and the negative genome. We model the effect of the icosahedral charge distribution from the protein shell instead of uniform using a mean-field theory. We find that the non-uniform charge distribution strongly affects the optimal genome length, and that it can explain the experimentally observed phenomenon of overcharging of virus and virus-like particles.

physics.bio-ph↗

arXiv2017

Energetically favoured defects in dense packings of particles on spherical surfaces

The dense packing of interacting particles on spheres has proved to be a useful model for virus capsids and colloidosomes. Indeed, icosahedral symmetry observed in virus capsids corresponds to potential energy minima that occur for magic numbers of, e.g., 12, 32 and 72 identical Lennard-Jones particles, for which the packing has exactly the minimum number of twelve five-fold defects. It is unclear, however, how stable these structures are against thermal agitation. We investigate this property by means of basin-hopping global optimisation and Langevin dynamics for particle numbers between ten and one hundred. An important measure is the number and type of point defects, that is, particles that do not have six nearest neighbours. We find that small icosahedral structures are the most robust against thermal fluctuations, exhibiting fewer excess defects and rearrangements for a wide temperature range. Furthermore, we provide evidence that excess defects appearing at low non-zero temperatures lower the potential energy at the expense of entropy. At higher temperatures defects are, as expected, thermally excited and thus entropically stabilised. If we replace the Lennard-Jones potential by a very short-ranged (Morse) potential, which is arguably more appropriate for colloids and virus capsid proteins, we find that the same particle numbers give a minimum in the potential energy, although for larger particle numbers these minima correspond to different packings. Furthermore, defects are more difficult to excite thermally for the short-ranged potential, suggesting that the short-ranged interaction further stabilises equilibrium structures.

cond-mat.soft↗

arXiv2017

Contact Mechanics of a Small Icosahedral Virus

Virus binding to a surface results at least locally, at the contact area, in stress and potential structural perturbation of the virus cage. Here we address the question of the role of substrate-induced deformation in the overall virus mechanical response to the adsorption event. This question may be especially important for the broad category of viruses that have their shells stabilized by weak, non-covalent interactions. We utilize atomic force microscopy to measure the height change distributions of the brome mosaic virus upon adsorption from liquid on atomically flat substrates and present a continuum model which captures well the behavior. Height data fitting according the model provides, without recourse to indentation, estimates of virus elastic properties and of the interfacial energy.

q-bio.QM↗

arXiv2016

In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway

HIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. There are two competing models for the process of forming the mature HIV-1 core: the disassembly and de novo reassembly model and the non-diffusional displacive model. To study the maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature particles and assembled virus-like particles with recombinant HIV-1 protease and monitor the process with biochemical assays and cryoEM structural analysis in parallel. Processing of Gag in vitro is accurate and efficient and results in both soluble capsid protein and conical or tubular capsid assemblies, seemingly converted from immature Gag particles. Computer simulations further reveal probable assembly pathways of HIV-1 capsid formation. Combining the experimental data and computer simulations, our results suggest a sequential combination of both displacive and disassembly/reassembly processes for HIV-1 maturation.

physics.bio-ph↗

arXiv2016

Functional analysis of the N-terminal basic motif of a eukaryotic satellite RNA virus capsid protein in replication and packaging

Efficient replication and assembly of virus particles are integral to the establishment of infection. In addition to the primary role of the capsid protein (CP) in encapsidating the RNA progeny, experimental evidence on positive sense single-stranded RNA viruses suggests that the CP also regulates RNA synthesis. Here, we demonstrate that replication of Satellite tobacco mosaic virus (STMV) is controlled by the cooperative interaction between STMV CP and the helper virus (HV) Tobacco mosaic virus (TMV) replicase. We identified that the STMV CP-HV replicase interaction requires a positively charged residue at the third position (3R) in the N-terminal 13 amino acid (aa) motif. Far-Northwestern blotting showed that STMV CP promotes binding between HV-replicase and STMV RNA. An STMV CP variant having an arginine to alanine substitution at position 3 in the N-terminal 13aa motif abolished replicase-CP binding. The N-terminal 13aa motif of the CP bearing alanine substitutions for positively charged residues located at positions 5, 7, 10 and 11 are defective in packaging full-length STMV, but can package a truncated STMV RNA lacking the 3' terminal 150 nt region. These findings provide insights into the mechanism underlying the regulation of STMV replication and packaging.

physics.bio-ph↗

arXiv2016

Effects of RNA branching on the electrostatic stabilization of viruses

Many single-stranded (ss) RNA viruses self assemble from capsid protein subunits and the nucleic acid to form an infectious virion. It is believed that the electrostatic interactions between the negatively charged RNA and the positively charged viral capsid proteins drive the encapsidation, although there is growing evidence that the sequence of the viral RNA also plays a role in packaging. In particular the sequence will determine the possible secondary structures that the ssRNA will take in solution. In this work, we use a mean field theory to investigate how the secondary structure of the RNA combined with electrostatic interactions affects the efficiency of assembly and stability of the assembled virions. We show that the secondary structure of RNA may result in negative osmotic pressures while a linear polymer causes positive osmotic pressures for the same conditions. This may suggest that the branched structure makes the RNA more effectively packaged and the virion more stable.

physics.bio-ph↗

arXiv2016

Recent advances in coarse-grained modeling of virus assembly

In many virus families, tens to thousands of proteins assemble spontaneously into a capsid (protein shell) while packaging the genomic nucleic acid. This review summarizes recent advances in computational modeling of these dynamical processes. We present an overview of recent technological and algorithmic developments, which are enabling simulations to describe the large ranges of length-and time-scales relevant to assembly, under conditions more closely matched to experiments than in earlier work. We then describe two examples in which computational modeling has recently provided an important complement to experiments.

q-bio.BM↗

arXiv2016

Role of Genome in the Formation of Conical Retroviral Shells

Human immunodeficiency virus (HIV) capsid proteins spontaneously assemble around the genome into a protective protein shell called the capsid, which can take on a variety of shapes broadly classified as conical, cylindrical and irregular. The majority of capsids seen in in vivo studies are conical in shape, while in vitro experiments have shown a preference for cylindrical capsids. The factors involved in the selection of the unique shape of HIV capsids are not well understood, and in particular the impact of RNA on the formation of the capsid is not known. In this work, we study the role of the genome and its interaction with the capsid protein by modeling the genomic RNA through a mean-field theory. Our results show that the confinement free energy for a homopolymeric model genome confined in a conical capsid is lower than that in a cylindrical capsid, at least when the genome does not interact with the capsid, which seems to be the case in in vivo experiments. Conversely, the confinement free energy for the cylinder is lower than for a conical capsid if the genome is attracted to the capsid proteins as the in vitro experiments. Understanding the factors that contribute to the formation of conical capsids may shed light on the infectivity of HIV particles.

physics.bio-ph↗

arXiv2016

RNA topology remolds electrostatic stabilization of viruses

Simple RNA viruses efficiently encapsulate their genome into a nano-sized protein shell: the capsid. Spontaneous co-assembly of the genome and the capsid proteins is driven predominantly by electrostatic interactions between the negatively charged RNA and the positively charged inner capsid wall. Using field theoretic formulation we show that the inherently branched RNA secondary structure allows viruses to maximize the amount of encapsulated genome and make assembly more efficient, allowing viral RNAs to out-compete cellular RNAs during replication in infected host cells.

physics.bio-ph↗

arXiv2015

Adsorption of annealed branched polymers on curved surfaces

The behavior of annealed branched polymers near adsorbing surfaces plays a fundamental role in many biological and industrial processes. Most importantly single stranded RNA in solution tends to fold up and self-bind to form a highly branched structure. Using a mean field theory, we both perturbatively and numerically examine the adsorption of branched polymers on surfaces of several different geometries in a good solvent. Independent of the geometry of the wall, we observe that as branching density increases, surface tension decreases. However, we find a coupling between the branching density and curvature in that a further lowering of surface tension occurs when the wall curves towards the polymer, but the amount of lowering of surface tension decreases when the wall curves away from the polymer. We find that for branched polymers confined into spherical cavities, most of branch-points are located in the vicinity of the interior wall and the surface tension is minimized for a critical cavity radius. For branch polymers next to sinusoidal surfaces, we find that branch-points accumulate at the valleys while end-points on the peaks.

cond-mat.soft↗

arXiv2014

A novel minimal in vitro system for analyzing HIV-1 Gag mediated budding

A biomimetic minimalist model membrane was used to study the mechanism and kinetics of cell-free in vitro HIV-1 Gag budding from a giant unilamellar vesicle (GUV). Real time interaction of Gag, RNA and lipid leading to the formation of mini-vesicles was measured using confocal microscopy. Gag forms resolution limited punctae on the GUV lipid membrane. Introduction of the Gag and urea to a GUV solution containing RNA led to the budding of mini-vesicles on the inside surface of the GUV. The GUV diameter showed a linear decrease in time due to bud formation. Both bud formation and decrease in GUV size were proportional to Gag concentration. In the absence of RNA, addition of urea to GUVs incubated with Gag also resulted in subvesicle formation but exterior to the surface. These observations suggest the possibility that clustering of GAG proteins leads to membrane invagination even in the absence of host cell proteins. The method presented here is promising, and allows for systematic study of the dynamics of assembly of immature HIV and help classify the hierarchy of factors that impact the Gag protein initiated assembly of retroviruses such as HIV.

physics.bio-ph↗

arXiv2014

The robust assembly of small symmetric nano-shells

Highly symmetric nano-shells are found in many biological systems, such as clathrin cages and viral shells. Several studies have shown that symmetric shells appear in nature as a result of the free energy minimization of a generic interaction between their constituent subunits. We examine the physical basis for the formation of symmetric shells, and using a minimal model we demonstrate that these structures can readily grow from identical subunits under non equilibrium conditions. Our model of nano-shell assembly shows that the spontaneous curvature regulates the size of the shell while the mechanical properties of the subunit determines the symmetry of the assembled structure. Understanding the minimum requirements for the formation of closed nano-shells is a necessary step towards engineering of nano-containers, which will have far reaching impact in both material science and medicine.

cond-mat.soft↗