Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

10-POS Board 10 Spatially Controlled Activation of Epha2 by Ephrina1 Increase Contractility and Integrin Adhesion Dynamics Zhongwen Chen . Mechanobiology Institute, Singapore, Please Select, Singapore. Eph receptors comprise the largest family of receptor tyrosine kinases. Together with their ligand Ephrin which is expressed on the neighboring cells, they form juxtacrine signaling. Specifically, EphA2 receptor is overexpressed in most of malignant breast cancers. There is a long debate about its role in cancer progression and many results seem contradictory, such as if it is pro- or anti-migratory. Recent studies of Eph signaling are beginning to reveal spatio-mechanical aspects of regulation and further resolution of these facets of regulation may explain the complex role of Eph signaling in cancer. In this study, we developed a spatially patterned hybrid substrate with fluid ephrinA1 ligands presented on supported lipid bilayers patches embedded within regions of immobilized RGD peptides, functioning as both integrin ligands and lipid bilayer barriers. With this, we successfully activate EphA2 receptors in a membrane-membrane configuration while maintaining cell-matrix interactions to activate integrin adhesion formation. This system allows detailed spatially resolved studies of both Eph- and Integrin- signaling activities, and enables direct observation of the influence of Eph signaling on integrin behavior. We found that ligand dependent activation of EphA2 receptors induce local myosin contractions and increase a more global integrin adhesion dynamics, which are in agreement with a migratory phenotype. The increase in integrin adhesion dynamics is dependent on activation of Src in EphA2 receptors, and follows Src/FAK/Paxillin signaling axis. Our results suggest that spatially controlled activation of EphA2 is pro-migratory through crosstalk with integrin.

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