Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Thursday Speaker Abstracts

CADHERIN-COATED EMULSIONS AS BIOMIMETIC TISSUES Jasna Brujic New York University, New York, New York, USA No Abstract

MOLECULAR FORCE TRANSDUCTION AT INTERCELLULAR ADHESIONS Deborah Leckband 1 ; 1 University of Illinois, Champaign-Urbana, IL, USA 2 University of California at San Diego, La Jolla, CA, USA 3 Johns Hopkins University, Baltimore, MD, USA Deborah Leckband 1 , Brendan Sullivan 1 , Ismaeel Muhamed 1 , Poonam Seghal 1 , Taejin Kim 1 , Yingxiao Wang 2 , Kalina Hristova 3 , Taylor Light 3 . 1. University of Illinois at Urbana-Champaign, IL. 2. University of California at San Diego, La Jolla, CA 3. Johns Hopkins University, Baltimore, MD The broad goal of these studies is to identify molecular mechanisms by which protein nanomachines at cadherin-based intercellular junctions transduce force. We use quantitative fluorescence imaging, in conjunction with mechanical measurements such as magnetic twisting cytometry and traction force microscopy to identify rapid, early molecular events in intercellular force transduction. Alpha catenin is a demonstrated force transducer at intercellular junctions that mechanically couples cadherins to F-actin. We engineered a FRET-based conformation sensor to visualize force-dependent conformation changes in alpha catenin in live cells. Dynamic fluorescence imaging demonstrated that alpha catenin undergoes a force-dependent conformational change at stressed intercellular junctions that facilitates the slower recruitment of an actin binding protein vinculin and the subsequent, local actin remodeling. Using these approaches, we also identified a second cadherin-mediated force transduction mechanism in epithelia. In this second mechanism, perturbing cadherin receptors activates epidermal growth factor receptor signaling and downstream integrins. Studies suggest that increased tension on cadherin bonds induces the disruption of growth factor receptor complexes at the plasma membrane to potentiate EGF-dependent signaling. Both mechano-transduction mechanisms require alpha catenin, which is required for cadherin-mediated force transmission. However each mechanism triggers distinct molecular cascades with different effects on cell mechanics. In conclusion, these results demonstrate two different molecular mechanisms by which proteins transduce force at intercellular adhesions. One involves the force-actuated conformation change in alpha catenin. In the second, increased force on cadherin bonds actuates growth factor receptor signaling, by disrupting protein-protein interactions.

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