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

Aida Nonn; Bálint Kiss; Weria Pezeshkian; Thomas Tancogne-Dejean; Albert Cerrone; Miklos Kellermayer; Yuanli Bai; Wei Li; Tomasz Wierzbicki

doi:10.1016/j.jmbbm.2023.106153

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

J Mech Behav Biomed Mater. 2023 Dec:148:106153. doi: 10.1016/j.jmbbm.2023.106153. Epub 2023 Oct 8.

Authors

Aida Nonn¹, Bálint Kiss², Weria Pezeshkian³, Thomas Tancogne-Dejean⁴, Albert Cerrone⁵, Miklos Kellermayer², Yuanli Bai⁶, Wei Li⁷, Tomasz Wierzbicki⁷

Affiliations

¹ CMM Lab, Faculty of Mechanical Engineering, OTH Regensburg, 93053, Regensburg, Germany. Electronic address: aida.nonn@oth-regensburg.de.
² Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, H-1094, Hungary; ELKH-SE Biophysical Virology Research Group, Budapest, H-1094, Hungary.
³ Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100, Copenhagen, Denmark.
⁴ Department of Mechanical and Process Engineering, ETH Zurich, 8050, Zurich, Switzerland.
⁵ Computational Hydraulics Laboratory, University of Notre Dame, Notre Dame, IN, 46556, USA.
⁶ Department of Mechanical and Aerospace of Engineering, University of Central Florida, 4000 Central Florida Blvd., Orlando, FL, 32816, USA.
⁷ Impact and Crashworthiness Lab, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

PMID: 37865016
DOI: 10.1016/j.jmbbm.2023.106153

Abstract

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.

Keywords: Coronavirus; Finite element analysis (FEA); Molecular dynamics (MD) simulation; Nanoindentation; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Elastic Modulus
Humans
Molecular Dynamics Simulation
SARS-CoV-2*