TY - JOUR
T1 - Effect of ionic strength on the assembly of simian vacuolating virus capsid protein around poly(styrene sulfonate)
AU - Asor, Roi
AU - Singaram, Surendra W.
AU - Levi-Kalisman, Yael
AU - Hagan, Michael F.
AU - Raviv, Uri
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to EDP Sciences, SIF and Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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. Graphic abstract: [Figure not available: see fulltext.].
AB - 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. Graphic abstract: [Figure not available: see fulltext.].
UR - http://www.scopus.com/inward/record.url?scp=85175738728&partnerID=8YFLogxK
U2 - 10.1140/epje/s10189-023-00363-x
DO - 10.1140/epje/s10189-023-00363-x
M3 - Article
C2 - 37917241
AN - SCOPUS:85175738728
SN - 1292-8941
VL - 46
JO - European Physical Journal E
JF - European Physical Journal E
IS - 11
M1 - 107
ER -