TY - JOUR

T1 - Inferring mechanical properties of the SARS-CoV-2 virus particle with nano-indentation tests and numerical simulations

AU - Nonn, Aida

AU - Kiss, Bálint

AU - Pezeshkian, Weria

AU - Tancogne-Dejean, Thomas

AU - Cerrone, Albert

AU - Kellermayer, Miklos

AU - Bai, Yuanli

AU - Li, Wei

AU - Wierzbicki, Tomasz

N1 - Publisher Copyright: © 2023 Elsevier Ltd

PY - 2023/10/8

Y1 - 2023/10/8

N2 - The pandemic caused by the SARS-CoV-2 virus has claimed more than 6.5 million lives worldwide. This global challenge has led to accelerated development of highly effective vaccines tied to their ability to elicit a sustained immune response. While numerous studies have focused primarily on the spike (S) protein, less is known about the interior of the virus. Here we propose a methodology that combines several experimental and simulation techniques to elucidate the internal structure and mechanical properties of the SARS-CoV-2 virus. The mechanical response of the virus was analyzed by nanoindentation tests using a novel flat indenter and evaluated in comparison to a conventional sharp tip indentation. The elastic properties of the viral membrane were estimated by analytical solutions, molecular dynamics (MD) simulations on a membrane patch and by a 3D Finite Element (FE)-beam model of the virion's spike protein and membrane molecular structure. The FE-based inverse engineering approach provided a reasonable reproduction of the mechanical response of the virus from the sharp tip indentation and was successfully verified against the flat tip indentation results. The elastic modulus of the viral membrane was estimated in the range of 7–20 MPa. MD simulations showed that the presence of proteins significantly reduces the fracture strength of the membrane patch. However, FE simulations revealed an overall high fracture strength of the virus, with a mechanical behavior similar to the highly ductile behavior of engineering metallic materials. The failure mechanics of the membrane during sharp tip indentation includes progressive damage combined with localized collapse of the membrane due to severe bending. Furthermore, the results support the hypothesis of a close association of the long membrane proteins (M) with membrane-bound hexagonally packed ribonucleoproteins (RNPs). Beyond improved understanding of coronavirus structure, the present findings offer a knowledge base for the development of novel prevention and treatment methods that are independent of the immune system.

AB - The pandemic caused by the SARS-CoV-2 virus has claimed more than 6.5 million lives worldwide. This global challenge has led to accelerated development of highly effective vaccines tied to their ability to elicit a sustained immune response. While numerous studies have focused primarily on the spike (S) protein, less is known about the interior of the virus. Here we propose a methodology that combines several experimental and simulation techniques to elucidate the internal structure and mechanical properties of the SARS-CoV-2 virus. The mechanical response of the virus was analyzed by nanoindentation tests using a novel flat indenter and evaluated in comparison to a conventional sharp tip indentation. The elastic properties of the viral membrane were estimated by analytical solutions, molecular dynamics (MD) simulations on a membrane patch and by a 3D Finite Element (FE)-beam model of the virion's spike protein and membrane molecular structure. The FE-based inverse engineering approach provided a reasonable reproduction of the mechanical response of the virus from the sharp tip indentation and was successfully verified against the flat tip indentation results. The elastic modulus of the viral membrane was estimated in the range of 7–20 MPa. MD simulations showed that the presence of proteins significantly reduces the fracture strength of the membrane patch. However, FE simulations revealed an overall high fracture strength of the virus, with a mechanical behavior similar to the highly ductile behavior of engineering metallic materials. The failure mechanics of the membrane during sharp tip indentation includes progressive damage combined with localized collapse of the membrane due to severe bending. Furthermore, the results support the hypothesis of a close association of the long membrane proteins (M) with membrane-bound hexagonally packed ribonucleoproteins (RNPs). Beyond improved understanding of coronavirus structure, the present findings offer a knowledge base for the development of novel prevention and treatment methods that are independent of the immune system.

KW - Coronavirus

KW - Finite element analysis (FEA)

KW - Molecular dynamics (MD) simulation

KW - Nanoindentation

KW - SARS-CoV-2

U2 - 10.1016/j.jmbbm.2023.106153

DO - 10.1016/j.jmbbm.2023.106153

M3 - Journal article

C2 - 37865016

AN - SCOPUS:85174353012

VL - 148

JO - Journal of the Mechanical Behavior of Biomedical Materials

JF - Journal of the Mechanical Behavior of Biomedical Materials

SN - 1751-6161

M1 - 106153

ER -