341 research outputs found
Modeling Viral Capsid Assembly
I present a review of the theoretical and computational methodologies that
have been used to model the assembly of viral capsids. I discuss the
capabilities and limitations of approaches ranging from equilibrium continuum
theories to molecular dynamics simulations, and I give an overview of some of
the important conclusions about virus assembly that have resulted from these
modeling efforts. Topics include the assembly of empty viral shells, assembly
around single-stranded nucleic acids to form viral particles, and assembly
around synthetic polymers or charged nanoparticles for nanotechnology or
biomedical applications. I present some examples in which modeling efforts have
promoted experimental breakthroughs, as well as directions in which the
connection between modeling and experiment can be strengthened.Comment: 42 pages (single column), 24 figures. Will appear in: Advances in
Chemical Physics, vol. 155 (2013
Emergent Self-organization in Active Materials
Biological systems exhibit large-scale self-organized dynamics and structures
which enable organisms to perform the functions of life. The field of active
matter strives to develop and understand microscopically-driven nonequilibrium
materials, with emergent properties comparable to those of living systems. This
review will describe two recently developed classes of active matter systems,
in which simple building blocks --- self-propelled colloidal particles or
extensile rod-like particles --- self-organize to form macroscopic structures
with features not possible in equilibrium systems. We summarize the recent
experimental and theoretical progress on each of these systems, and we present
simple descriptions of the physics underlying their emergent behaviors.Comment: Submitted to Current Opinion in Cell Biology. 9 pages (including
references) and 3 figure
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.Comment: 9 pages, 3 figure
Diffusion-limited rates on low-dimensional manifolds with extreme aspect ratios
We consider a single-species diffusion-limited annihilation reaction with
reactants confined to a two-dimensional surface with one arbitrarily large
dimension and the other comparable in size to interparticle distances. This
situation could describe reactants which undergo both longitudinal and
transverse diffusion on long filamentous molecules (such as microtubules), or
molecules that undergo truly one-dimensional translational diffusion (e.g. a
transcription factor on DNA) but simultaneously exhibit diffusive behavior in a
second dimension corresponding to a rotational or conformational degree of
freedom. We combine simple analytical arguments and Monte Carlo simulations to
show that the reaction rate law exhibits a crossover from one-dimensional to
two-dimensional diffusion as a function of particle concentration and the size
of the smaller dimension. In the case of a reversible binding reaction, the
diffusion-limited reaction rate is given by the Smoluchowski expression, but
the crossover is revealed in the statistics of particle collision histories.
The results can also be applied to a particle-antiparticle annihilation
reaction.Comment: 6 pages, 4 figures, submitted to Phys. Rev.
Allosteric control in icosahedral capsid assembly
During the lifecycle of a virus, viral proteins and other components
self-assemble to form a symmetric protein shell called a capsid. This assembly
process is subject to multiple competing constraints, including the need to
form a thermostable shell while avoiding kinetic traps. It has been proposed
that viral assembly satisfies these constraints through allosteric regulation,
including the interconversion of capsid proteins among conformations with
different propensities for assembly. In this article we use computational and
theoretical modeling to explore how such allostery affects the assembly of
icosahedral shells. We simulate assembly under a wide range of protein
concentrations, protein binding affinities, and two different mechanisms of
allosteric control. We find that, above a threshold strength of allosteric
control, assembly becomes robust over a broad range of subunit binding
affinities and concentrations, allowing the formation of highly thermostable
capsids. Our results suggest that allostery can significantly shift the range
of protein binding affinities that lead to successful assembly, and thus should
be accounted for in models that are used to estimate interaction parameters
from experimental data.Comment: Bill Gelbart's Festschrif
Encapsulation of a polymer by an icosahedral virus
The coat proteins of many viruses spontaneously form icosahedral capsids
around nucleic acids or other polymers. Elucidating the role of the packaged
polymer in capsid formation could promote biomedical efforts to block viral
replication and enable use of capsids in nanomaterials applications. To this
end, we perform Brownian dynamics on a coarse-grained model that describes the
dynamics of icosahedral capsid assembly around a flexible polymer. We identify
several mechanisms by which the polymer plays an active role in its
encapsulation, including cooperative polymer-protein motions. These mechanisms
are related to experimentally controllable parameters such as polymer length,
protein concentration, and solution conditions. Furthermore, the simulations
demonstrate that assembly mechanisms are correlated to encapsulation
efficiency, and we present a phase diagram that predicts assembly outcomes as a
function of experimental parameters. We anticipate that our simulation results
will provide a framework for designing in vitro assembly experiments on
single-stranded RNA virus capsids.Comment: This is an author-created, un-copyedited version of an article
accepted for publication in Physical Biology. IOP Publishing Ltd is not
responsible for any errors or omissions in this version of the manuscript or
any version derived from it. The definitive publisher authenticated version
is expected to be published online in November 201
Mechanisms of virus assembly
Viruses are nanoscale entities containing a nucleic acid genome encased in a
protein shell called a capsid, and in some cases surrounded by a lipid bilayer
membrane. This review summarizes the physics that govern the processes by which
capsids assembles within their host cells and in vitro. We describe the
thermodynamics and kinetics for assembly of protein subunits into icosahedral
capsid shells, and how these are modified in cases where the capsid assembles
around a nucleic acid or on a lipid bilayer. We present experimental and
theoretical techniques that have been used to characterize capsid assembly, and
we highlight aspects of virus assembly which are likely to receive significant
attention in the near future.Comment: Submitted to Annual Review of Physical Chemistr
Dynamics of Self-Propelled Particles Under Strong Confinement
We develop a statistical theory for the dynamics of non-aligning,
non-interacting self-propelled particles confined in a convex box in two
dimensions. We find that when the size of the box is small compared to the
persistence length of a particle's trajectory (strong confinement), the
steady-state density is zero in the bulk and proportional to the local
curvature on the boundary. Conversely, the theory may be used to construct the
box shape that yields any desired density distribution on the boundary. When
the curvature variations are small, we also predict the distribution of
orientations at the boundary and the exponential decay of pressure as a
function of box size recently observed in 3D simulations in a spherical box.Comment: 6 pages, 5 figure
Faceted particles formed by the frustrated packing of anisotropic colloids on curved surfaces
We use computer simulations and simple theoretical models to analyze the
morphologies that result when rod-like particles end-attach onto a curved
surface, creating a finite-thickness monolayer aligned with the surface normal.
This geometry leads to two forms of frustration, one associated with the
incompatibility of hexagonal order on surfaces with Gaussian curvature, and the
second reflecting the deformation of a layer with finite thickness on a surface
with non-zero mean curvature. We show that the latter effect leads to a
faceting mechanism. Above threshold values of the inter-particle attraction
strength and surface mean curvature, the adsorbed layer undergoes a transition
from orientational disorder to an ordered state that is demarcated by
reproducible patterns of line defects. The number of facets is controlled by
the competition between line defect energy and intra-facet strain. Tuning
control parameters thus leads to a rich variety of morphologies, including
icosahedral particles and irregular polyhedra. In addition to suggesting a new
strategy for the synthesis of aspherical particles with tunable symmetries, our
results may shed light on recent experiments in which rod-like HIV GAG proteins
assemble around nanoscale particles.Comment: 9 pages, 8 figure
Active Particles on Curved Surfaces
Recent studies have highlighted the sensitivity of active matter to
boundaries and their geometries. Here we develop a general theory for the
dynamics and statistics of active particles on curved surfaces and illustrate
it on two examples. We first show that active particles moving on a surface
with no ability to probe its curvature only exhibit steady-state
inhomogeneities in the presence of orientational order. We then consider a
strongly confined 3D ideal active gas and compute its steady-state density
distribution in a box of arbitrary convex shape.Comment: 9 pages, 1 figur
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