Effect of ionic strength on the assembly of simian vacuolating virus capsid protein around poly(styrene sulfonate)

IF 1.8 4区 物理与天体物理 Q4 CHEMISTRY, PHYSICAL The European Physical Journal E Pub Date : 2023-11-02 DOI:10.1140/epje/s10189-023-00363-x
Roi Asor, Surendra W. Singaram, Yael Levi-Kalisman, Michael F. Hagan, Uri Raviv
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引用次数: 2

Abstract

Virus-like particles (VLPs) are noninfectious nanocapsules that can be used for drug delivery or vaccine applications. VLPs can be assembled from virus capsid proteins around a condensing agent, such as RNA, DNA, or a charged polymer. Electrostatic interactions play an important role in the assembly reaction. VLPs assemble from many copies of capsid protein, with a combinatorial number of intermediates. Hence, the mechanism of the reaction is poorly understood. In this paper, we combined solution small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (TEM), and computational modeling to determine the effect of ionic strength on the assembly of Simian Vacuolating Virus 40 (SV40)-like particles. We mixed poly(styrene sulfonate) with SV40 capsid protein pentamers at different ionic strengths. We then characterized the assembly product by SAXS and cryo-TEM. To analyze the data, we performed Langevin dynamics simulations using a coarse-grained model that revealed incomplete, asymmetric VLP structures consistent with the experimental data. We found that close to physiological ionic strength, \(T=1\) VLPs coexisted with VP1 pentamers. At lower or higher ionic strengths, incomplete particles coexisted with pentamers and \(T=1\) particles. Including the simulated structures was essential to explain the SAXS data in a manner that is consistent with the cryo-TEM images.

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离子强度对猿猴空泡化病毒衣壳蛋白在聚(苯乙烯磺酸盐)周围组装的影响。
病毒样颗粒(VLP)是一种非感染性纳米胶囊,可用于药物递送或疫苗应用。VLP可以由病毒衣壳蛋白围绕凝聚剂组装,如RNA、DNA或带电聚合物。静电相互作用在组装反应中起着重要作用。VLP由衣壳蛋白的许多拷贝组装而成,具有组合数量的中间体。因此,人们对该反应的机理知之甚少。在本文中,我们结合溶液小角度X射线散射(SAXS)、冷冻透射电子显微镜(TEM)和计算模型来确定离子强度对四面液泡病毒40(SV40)样颗粒组装的影响。我们在不同离子强度下将聚(苯乙烯磺酸盐)与SV40衣壳蛋白五聚体混合。然后,我们用SAXS和低温TEM对组装产物进行了表征。为了分析数据,我们使用粗粒度模型进行了Langevin动力学模拟,该模型揭示了与实验数据一致的不完整、不对称的VLP结构。我们发现,接近生理离子强度,[公式:见正文]VLP与VP1五聚体共存。在较低或较高的离子强度下,不完全粒子与五聚体和[公式:见正文]粒子共存。包括模拟结构对于以与低温TEM图像一致的方式解释SAXS数据至关重要。
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来源期刊
The European Physical Journal E
The European Physical Journal E CHEMISTRY, PHYSICAL-MATERIALS SCIENCE, MULTIDISCIPLINARY
CiteScore
2.60
自引率
5.60%
发文量
92
审稿时长
3 months
期刊介绍: EPJ E publishes papers describing advances in the understanding of physical aspects of Soft, Liquid and Living Systems. Soft matter is a generic term for a large group of condensed, often heterogeneous systems -- often also called complex fluids -- that display a large response to weak external perturbations and that possess properties governed by slow internal dynamics. Flowing matter refers to all systems that can actually flow, from simple to multiphase liquids, from foams to granular matter. Living matter concerns the new physics that emerges from novel insights into the properties and behaviours of living systems. Furthermore, it aims at developing new concepts and quantitative approaches for the study of biological phenomena. Approaches from soft matter physics and statistical physics play a key role in this research. The journal includes reports of experimental, computational and theoretical studies and appeals to the broad interdisciplinary communities including physics, chemistry, biology, mathematics and materials science.
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