DNA mechanotechnology reveals that integrin receptors apply pN forces in podosomes on fluid substrates

Roxanne Glazier, Joshua M. Brockman, Emily Bartle, Alexa L. Mattheyses, Olivier Destaing () and Khalid Salaita ()
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Roxanne Glazier: Georgia Institute of Technology and Emory University
Joshua M. Brockman: Georgia Institute of Technology and Emory University
Emily Bartle: University of Alabama at Birmingham
Alexa L. Mattheyses: University of Alabama at Birmingham
Olivier Destaing: Centre de Recherche Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309
Khalid Salaita: Georgia Institute of Technology and Emory University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Podosomes are ubiquitous cellular structures important to diverse processes including cell invasion, migration, bone resorption, and immune surveillance. Structurally, podosomes consist of a protrusive actin core surrounded by adhesion proteins. Although podosome protrusion forces have been quantified, the magnitude, spatial distribution, and orientation of the opposing tensile forces remain poorly characterized. Here we use DNA nanotechnology to create probes that measure and manipulate podosome tensile forces with molecular piconewton (pN) resolution. Specifically, Molecular Tension-Fluorescence Lifetime Imaging Microscopy (MT-FLIM) produces maps of the cellular adhesive landscape, revealing ring-like tensile forces surrounding podosome cores. Photocleavable adhesion ligands, breakable DNA force probes, and pharmacological inhibition demonstrate local mechanical coupling between integrin tension and actin protrusion. Thus, podosomes use pN integrin forces to sense and respond to substrate mechanics. This work deepens our understanding of podosome mechanotransduction and contributes tools that are widely applicable for studying receptor mechanics at dynamic interfaces.

Date: 2019
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DOI: 10.1038/s41467-019-12304-4

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