Assembly of viruses and the pseudo-law of mass action

Morozov, A. Yu.; Bruinsma, Robijn; Rudnick, Joseph

doi:10.1063/1.3212694

Cited by 60 publications

(58 citation statements)

References 14 publications

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“…Theoretical models of assembly reactions predict relatively high concentrations of intermediates early in the reaction that are depleted as the assembly reaction progresses, 16,18–21,40 which is in agreement with our findings. At dimer concentrations near the pseudo-critical concentration (0.5 – 1 µM), we observed robust capsid formation with a transient, low concentration of intermediates (Figure S3 in the Supporting Information).…”

Section: Discussionsupporting

confidence: 91%

Monitoring Assembly of Virus Capsids with Nanofluidic Devices

et al. 2015

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Virus assembly is a coordinated process in which typically hundreds of subunits react to form complex, symmetric particles. We use resistive-pulse sensing to characterize the assembly of Hepatitis B Virus core protein dimers into T = 3 and T = 4 icosahedral capsids. This technique counts and sizes intermediates and capsids in real time, with single particle sensitivity, and at biologically relevant concentrations. Other methods are not able to produce comparable real-time, single-particle observations of assembly reactions below, near, and above the pseudocritical dimer concentration, at which the dimer and capsid concentrations are approximately equal. Assembly reactions across a range of dimer concentrations reveal three distinct patterns. At dimer concentrations as low as 50 nM, well below the pseudo-critical dimer concentration of 0.5 µM, we observe a switch in the ratio of T = 3 to T = 4 capsids, which increases with decreasing dimer concentration. Far above the pseudo-critical dimer concentration, kinetically trapped, incomplete T = 4 particles assemble rapidly, then slowly anneal into T = 4 capsids. At all dimer concentrations tested, T = 3 capsids form more rapidly than T = 4 capsids, suggesting distinct pathways for the two forms.

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Section: Discussionsupporting

confidence: 91%

Monitoring Assembly of Virus Capsids with Nanofluidic Devices

et al. 2015

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“…Since our discrete, finite-size stochastic model captures many features expected in cell and molecular processes, the results illustrated in this work may influence many processes including telomere clustering in the yeast nuclei, 17,34,35 filament 16 and viral capsid assembly, 36 amyloid polymerization, 18,20,37 and claritin coating of vesicles. 38,39 Moreover, the mechanisms we describe may contribute to observed effects in self-assembly, such as sample volume-dependent lag times for the formation of critical nuclei.…”

Section: Discussionmentioning

confidence: 99%

First assembly times and equilibration in stochastic coagulation-fragmentation

D’Orsogna¹,

Lei

Chou

2015

The Journal of Chemical Physics

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We develop a fully stochastic theory for coagulation and fragmentation (CF) in a finite system with a maximum cluster size constraint. The process is modeled using a high-dimensional master equation for the probabilities of cluster configurations. For certain realizations of total mass and maximum cluster sizes, we find exact analytical results for the expected equilibrium cluster distributions. If coagulation is fast relative to fragmentation and if the total system mass is indivisible by the mass of the largest allowed cluster, we find a mean cluster-size distribution that is strikingly broader than that predicted by the corresponding mass-action equations. Combinations of total mass and maximum cluster size under which equilibration is accelerated, eluding late-stage coarsening, are also delineated. Finally, we compute the mean time it takes particles to first assemble into a maximum-sized cluster. Through careful state-space enumeration, the scaling of mean assembly times is derived for all combinations of total mass and maximum cluster size. We find that CF accelerates assembly relative to monomer kinetic only in special cases. All of our results hold in the infinite system limit and can be only derived from a high-dimensional discrete stochastic model, highlighting how classical mass-action models of self-assembly can fail. C 2015 AIP Publishing LLC. [http://dx

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“…26 Similar ideas have been developed by Zlotnick and others in order to describe viral capsid assembly. 38,39,[43][44][45][46] In this section, we show that non-monotonic steadystate yields Y ss can be predicted by such equations, but we emphasise that these equations fail to capture the decreasing quality Q prod that occurs in both capsid and lattice gas models. We argue that this failure of kinetic rate equations is linked with the breakdown of the cluster equilibration condition (5).…”

Section: Kinetic Equations In Self-assemblymentioning

confidence: 99%

Mechanisms of kinetic trapping in self-assembly and phase transformation

Hagan

Elrad

Jack

2011

The Journal of Chemical Physics

110

152

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In self-assembly processes, kinetic trapping effects often hinder the formation of thermodynamically stable ordered states. In a model of viral capsid assembly and in the phase transformation of a lattice gas, we show how simulations in a self-assembling steady state can be used to identify two distinct mechanisms of kinetic trapping. We argue that one of these mechanisms can be adequately captured by kinetic rate equations, while the other involves a breakdown of theories that rely on cluster size as a reaction coordinate. We discuss how these observations might be useful in designing and optimising self-assembly reactions.

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Assembly of viruses and the pseudo-law of mass action

Cited by 60 publications

References 14 publications

Monitoring Assembly of Virus Capsids with Nanofluidic Devices

Monitoring Assembly of Virus Capsids with Nanofluidic Devices

First assembly times and equilibration in stochastic coagulation-fragmentation

Mechanisms of kinetic trapping in self-assembly and phase transformation

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