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Probing Integrin Specificity in regards to Clustering Dynamics on Soft and Stiff Matrices

  • Author(s): Gile, Ryan Edward
  • Advisor(s): Weaver, Valerie M
  • et al.
Abstract

Integrins are key sensory molecules that transduce chemical and physical cues from the extracellular matrix (ECM) to initiate biochemical signaling and cytoskeletal remodeling to regulate cell behavior and tissue structure. These transmembrane cell-ECM receptors occur as distinct types and drive different cell and tissue level behaviors and consequently also contribute non uniformly to their pathologies. To act integrins cluster in the plasma membrane and recruit scaffolding and signaling molecules required for the mechanical and biochemical functions performed by adhesion-plaques. Regulation of integrin clustering by the material properties of the ECM has been suggested to be a fundamental processes employed by cells to sense and respond to their mechanical environment. However, the molecular mechanisms that drive clustering in response to interaction with the ECM remain unclear. Recent studies have demonstrated a direct link between integrin clustering, increased matrix stiffness, and breast cancer. Additionally data from primary breast cancers suggests alpha5-integrin drives invasion while alpha2-integrin acts as a tumor suppressor. Integrin alpha5 is known to have special mechanical properties but recent work on integrin recycling suggests its dynamics may be very different as well. This study employs the high resolution imaging technique of fluorescence recovery after photobleaching (FRAP) to measure and compare the clustering dynamics of alpha5-integrin and alpha2-integrin in the non malignant mammary epithelial cell line MCF10A cultured on polyacrylamide gels mechanically tuned to match the compliances exhibited by healthy and pathologic breast tissue.

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