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

Nature Communications, 2020

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.

Gold nanospheres (9 ± 2 nm, 0.05 mg ml−1 in tannic acid) produced by our partner nanoComposix are featured in this study.