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Mechanobiology of Disease
Poster Abstracts
47
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.