DYNAMICS AND ORGANIZATION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR INVESTIGATED BY IMAGING FLUORESCENCE CORRELATION SPECTROSCOPY

Abstract

Epidermal Growth Factor Receptor (EGFR) as a prototypical receptor tyrosine kinase is intensively studied due to its important role in aberrant cancer signaling. Despite many years study, the exact activation mechanism is still not clear especially the dynamics and organization of EGFR on the plasma membrane which regulate its activation remains as a challenge due to technique limitations. The development of Imaging Fluorescence Correlation Spectroscopy (FCS), a quantitative bioimaging tool, enables measuring both the dynamics and organization of EGFR with single molecule sensitivity. The diffusion and spatial localization of EGFR at its resting and activated states in live cell membrane is explored by employing this new modality. Implementation of Imaging diffusion law analysis provides information of nanoscale organization of EGFR. The results in this thesis provide new insights into spatial-temporal dynamics of EGFR which help to better understand its role in health and diseases.