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Sci Rep. 2019 Jan 22;9(1):267. doi: 10.1038/s41598-018-36449-2.

Biomechanical characterization of TIM protein-mediated Ebola virus-host cell adhesion.

Author information

1
Department of Mechanical Engineering & Mechanics, Lehigh University, 19 Memorial Drive West, Bethlehem, PA, 18015, USA.
2
Department of Medicine, Rheumatology, Columbia University Medical Center, New York, NY, 10032, USA.
3
Department of Chemical and Biomolecular Engineering, Lehigh University, 111 Research Drive, Bethlehem, PA, 18015, USA.
4
Department of Bioengineering, Lehigh University, 111 Research Drive, Bethlehem, PA, 18015, USA.
5
Preclinical Research, Cresilon, 122 18th Street, New York, NY, 11215, USA.
6
Acoustics division, Apple Inc., One Apple Park Way, Cupertino, CA, 95014, USA.
7
Department of Microbiology, University of Iowa, 51 Newton Rd, Iowa City, IA, 52242, USA.
8
Department of Mechanical Engineering & Mechanics, Lehigh University, 19 Memorial Drive West, Bethlehem, PA, 18015, USA. frank.zhang@lehigh.edu.
9
Department of Bioengineering, Lehigh University, 111 Research Drive, Bethlehem, PA, 18015, USA. frank.zhang@lehigh.edu.

Abstract

Since the most recent outbreak, the Ebola virus (EBOV) epidemic remains one of the world's public health and safety concerns. EBOV is a negative-sense RNA virus that can infect humans and non-human primates, and causes hemorrhagic fever. It has been proposed that the T-cell immunoglobulin and mucin domain (TIM) family proteins act as cell surface receptors for EBOV, and that the interaction between TIM and phosphatidylserine (PS) on the surface of EBOV mediates the EBOV-host cell attachment. Despite these initial findings, the biophysical properties of the TIM-EBOV interaction, such as the mechanical strength of the TIM-PS bond that allows the virus-cell interaction to resist external mechanical perturbations, have not yet been characterized. This study utilizes single-molecule force spectroscopy to quantify the specific interaction forces between TIM-1 or TIM-4 and the following binding partners: PS, EBOV virus-like particle, and EBOV glycoprotein/vesicular stomatitis virus pseudovirion. Depending on the loading rates, the unbinding forces between TIM and ligands ranged from 40 to 100 pN, suggesting that TIM-EBOV interactions are mechanically comparable to previously reported adhesion molecule-ligand interactions. The TIM-4-PS interaction is more resistant to mechanical force than the TIM-1-PS interaction. We have developed a simple model for virus-host cell interaction that is driven by its adhesion to cell surface receptors and resisted by membrane bending (or tension). Our model identifies critical dimensionless parameters representing the ratio of deformation and adhesion energies, showing how single-molecule adhesion measurements relate quantitatively to the mechanics of virus adhesion to the cell.

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