title: A new strategy to measure intercellular adhesion forces in mature cell-cell contacts.
abstract: Intercellular adhesion plays a major role in tissue development and homeostasis. Yet, technologies to measure mature cell-cell contacts are not available. We introduce a methodology based on fluidic probe force microscopy to assess cell-cell adhesion forces after formation of mature intercellular contacts in cell monolayers. With this method we quantify that L929 fibroblasts exhibit negligible cell-cell adhesion in monolayers whereas human endothelial cells from the umbilical artery (HUAECs) exert strong intercellular adhesion forces per cell. We use a new in vitro model based on the overexpression of Muscle Segment Homeobox 1 (MSX1) to induce Endothelial-to-Mesenchymal Transition (EndMT), a process involved in cardiovascular development and disease. We reveal how intercellular adhesion forces in monolayer decrease significantly at an early stage of EndMT and we show that cells undergo stiffening and flattening at this stage. This new biomechanical insight complements and expands the established standard biomolecular analyses. Our study thus introduces a novel tool for the assessment of mature intercellular adhesion forces in a physiological setting that will be of relevance to biological processes in developmental biology, tissue regeneration and diseases like cancer and fibrosis.
authors.affiliation: Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute (BPI), University of Würzburg, 97070 Würzburg, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Sancho
authors.affiliation: Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Ine
authors.initials: I
authors.lastname: Vandersmissen
authors.affiliation: Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Sander
authors.initials: S
authors.lastname: Craps
authors.affiliation: Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.affiliation: Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute (BPI), University of Würzburg, 97070 Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Groll
mesh_terms: D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002450:Cell Communication; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D051957:MSX1 Transcription Factor / Q000378:metabolism; D014469:Umbilical Arteries / Q000166:cytology; D015854:Up-Regulation
chemical_list: D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human