Protrusion force microscopy reveals oscillatory force generation and mechanosensing activity of human macrophage podosomes

Anna Labernadie, Anaïs Bouissou, Patrick Delobelle, Stéphanie Balor, Raphael Voituriez, Amsha Proag, Isabelle Fourquaux, Christophe Thibault, Christophe Vieu, Renaud Poincloux, Guillaume M. Charrière () and Isabelle Maridonneau-Parini ()
Additional contact information
Anna Labernadie: CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale)
Anaïs Bouissou: CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale)
Patrick Delobelle: FEMTO-ST, UMR CNRS 6174, Université de Franche Comté
Stéphanie Balor: Plateau Microscopie électronique, IEFG CNRS IFR 109, Bat. IBCG
Raphael Voituriez: CNRS UMR7600, Université Pierre et Marie Curie
Amsha Proag: CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale)
Isabelle Fourquaux: Centre de Microscopie Électronique Appliquée à la Biologie, Faculté de Médecine de Rangueil
Christophe Thibault: CNRS-LAAS (Laboratoire d’Analyse et d’Architecture des Systèmes)
Christophe Vieu: CNRS-LAAS (Laboratoire d’Analyse et d’Architecture des Systèmes)
Renaud Poincloux: CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale)
Guillaume M. Charrière: CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale)
Isabelle Maridonneau-Parini: CNRS-IPBS (Institut de Pharmacologie et de Biologie Structurale)

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Podosomes are adhesion structures formed in monocyte-derived cells. They are F-actin-rich columns perpendicular to the substrate surrounded by a ring of integrins. Here, to measure podosome protrusive forces, we designed an innovative experimental setup named protrusion force microscopy (PFM), which consists in measuring by atomic force microscopy the deformation induced by living cells onto a compliant Formvar sheet. By quantifying the heights of protrusions made by podosomes onto Formvar sheets, we estimate that a single podosome generates a protrusion force that increases with the stiffness of the substratum, which is a hallmark of mechanosensing activity. We show that the protrusive force generated at podosomes oscillates with a constant period and requires combined actomyosin contraction and actin polymerization. Finally, we elaborate a model to explain the mechanical and oscillatory activities of podosomes. Thus, PFM shows that podosomes are mechanosensing cell structures exerting a protrusive force.

Date: 2014
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DOI: 10.1038/ncomms6343

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