Forces during cellular uptake of viruses and nanoparticles at the ventral side

Tina Wiegand (), Marta Fratini, Felix Frey, Klaus Yserentant, Yang Liu, Eva Weber, Kornelia Galior, Julia Ohmes, Felix Braun, Dirk-Peter Herten, Steeve Boulant, Ulrich S. Schwarz, Khalid Salaita, E. Ada Cavalcanti-Adam () and Joachim P. Spatz ()
Additional contact information
Tina Wiegand: Max Planck Institute for Medical Research
Marta Fratini: Max Planck Institute for Medical Research
Felix Frey: BioQuant Center, Heidelberg University
Klaus Yserentant: Heidelberg University
Yang Liu: Emory University
Eva Weber: Max Planck Institute for Medical Research
Kornelia Galior: Emory University
Julia Ohmes: Max Planck Institute for Medical Research
Felix Braun: Heidelberg University
Dirk-Peter Herten: Heidelberg University
Steeve Boulant: University Hospital
Ulrich S. Schwarz: BioQuant Center, Heidelberg University
Khalid Salaita: Emory University
E. Ada Cavalcanti-Adam: Max Planck Institute for Medical Research
Joachim P. Spatz: Max Planck Institute for Medical Research

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Many intracellular pathogens, such as mammalian reovirus, mimic extracellular matrix motifs to specifically interact with the host membrane. Whether and how cell-matrix interactions influence virus particle uptake is unknown, as it is usually studied from the dorsal side. Here we show that the forces exerted at the ventral side of adherent cells during reovirus uptake exceed the binding strength of biotin-neutravidin anchoring viruses to a biofunctionalized substrate. Analysis of virus dissociation kinetics using the Bell model revealed mean forces higher than 30 pN per virus, preferentially applied in the cell periphery where close matrix contacts form. Utilizing 100 nm-sized nanoparticles decorated with integrin adhesion motifs, we demonstrate that the uptake forces scale with the adhesion energy, while actin/myosin inhibitions strongly reduce the uptake frequency, but not uptake kinetics. We hypothesize that particle adhesion and the push by the substrate provide the main driving forces for uptake.

Date: 2020
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DOI: 10.1038/s41467-019-13877-w

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