Integrin-mediated sensing of the biochemical and biophysical properties of the extracellular matrix (ECM) allows cells to control adhesion and signaling. Currently, the understanding begins to emerge how different integrins binding to the same ECM ligand cooperate during adhesion initiation and how cells sense and respond to mechanical cues immediately upon ligand-binding. I will report how fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin during adhesion initiation in a biphasic manner. In moderate load regime, fibronectin-engaged α5β1 integrins sense mechanical load via catch bonds and immediately trigger signaling cascades. These activate additional integrins to bind fibronectin. If the mechanical load applied to fibronectin-bound α5β1 integrins exceeds a threshold, bond properties of these integrins change. In this high load regime, fibroblasts fail to activate additional integrins. This unique response to mechanical load regulates integrin-mediated adhesion much before visible adhesion clusters assemble. Additionally, I will discuss biochemical regulations of α5β1 integrins conformation and function in different stages of adhesion initiation to fibronectin. I will report that αVβ3 integrins first outcompete α5β1 integrins for ligand binding and later induce signaling cascades that increases α5β1 integrin clustering. The discussed results highlight how fibronectin-binding integrins coordinate adhesion initiation of fibroblasts to fibronectin via diverse signaling pathways and how these can be used to control cellular attachment.

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Bio

Dr. Nico Strohmeyer received his diploma degree at Technical University of Freiberg in 2011 in natural sciences. In 2017 he obtained his PhD degree in cellular biophysics 2017 under the supervision of Prof. Daniel Müller in the Department of Biosystems Science and Engineering, ETH Zürich. Since 2018 he continued his research as postdoc together with Daniel Müller and Reinhard Fässler at ETH Zürich. His main research interest is to understand how adhesion of cells is initiated and how this affects cellular behavior.