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

• Type of Material: Article
• Authors: Tina Wiegand, Max Planck Institute for Medical Research; Marta Fratini, Max Planck Institute for Medical Research; Felix Frey, Heidelberg University; Klaus Yserentant, Heidelberg University; Yang Liu, Emory University; Eva Weber, Max Planck Inst Med ResMax Planck Institute for Medical Research; Komelia Galior, Emory University; Julia Ohmes, Max Planck Institute for Medical Research; Felix Braun, Heidelberg University; Dirk-Peter Herten, Heidelberg University; Steeve Boulant, German Cancer Research Center; Ulrich S. Schwarz, 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
• Language: English
• Date: 2020-01-02
• Publisher: NATURE PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © 2020, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-019-13877-w
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 11
• Issue: 1
• Start Page: 32
• End Page: 32
• Grant/Funding Information: This work was supported by the German Science Foundation (SFB1129 project P15 to E.A.C.-A. and J.P.S., P14 to S.B. and P4 to U.S.S., EXC81 to D.-P.H.), the BMBF/VDI (MorphiQuant3D to D.-P.H.) and the Max Planck Society. T.W. was supported by the Boehringer-Ingelheim Foundation. F.F. was supported by the Heidelberg Graduate School for Fundamental Physics (HGSFP).
• Keywords: GOLD NANOPARTICLES; SURFACE; Multidisciplinary Sciences; AVIDIN BINDING; Science & Technology; Science & Technology - Other Topics; ENDOCYTOSIS; KINETICS; PARTICLES; REOVIRUS; ADHESION; PROTEIN; HEPARAN-SULFATE
• Research Categories: Biology, Cell; Biology, Virology

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.