Modeling and Tracking Glycan Diffusion Near Integrin Adhesions Using Biorthogonal Click-Chemistry and Interference Microscopy

Status: This talk is in preparation - details may change

The dynamics of integrin adhesion to the extracellular matrix (ECM) is critical for cell motility and growth, yet metastatic cells are capable of anchorage-independent survival with loss of adhesion from the primary tumor and subsequent adhesion in the microenvironment of the metastatic niche. Unfortunately, we do not yet have a clear
understanding of the detailed mechanisms that govern the nucleation, clustering and adhesion of integrins to the ECM in the presence of the myriad of cell-surface glycoproteins that extend into the extracellular space. In order to explore how interactions between integrins and glycans alter clustering and adhesion, we have adopted a three-pronged approach that includes: (1) modeling the energetic landscape that governs membrane bending and integrin adhesion; (2) tracking bioorthogonally tagged cell-surface glycans with single-molecule sensitivity and (3) measuring membrane topography using phase-shifted laser feedback interference microscopy.