Berlin 2005 – wissenschaftliches Programm

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AKB: Biologische Physik

AKB 200: Poster Session II

AKB 200.51: Poster

Dienstag, 8. März 2005, 17:00–19:00, Poster TU C

Complex and dynamic estrogen receptor-α interactions in living cells revealed by diffusion-time distribution analysis — •Michael Prummer, Hanna Jankevics, Paulina Izewska, Horst Pick, Kirsten Leufgen, and Horst Vogel — Laboratory of Physical Chemistry of Polymers and Membranes, Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland

Specific binding of ligands induce characteristic mobility patterns of human estrogen receptor-α (ER) in living breast cancer cells. These patterns were determined by analyzing the distribution of diffusion times obtained from fluorescence correlation spectroscopy experiments of ER conjugated to yellow fluorescent protein (YFP). The highly mobile ER in untreated cells slowed down in the presence of agonist and partial antagonist. The reduced mobility was accompanied by the formation of multiple discrete states in a broad distribution of diffusion times, where different states were observed for different ligands. This new finding reveals that ER forms a limited number of complexes with different mobility and varying population by dynamic interaction with many other nuclear components with well defined interaction times. Our approach to examine ER interactions at native expression levels opens up new routes to elucidate hormone-dependent transcription regulation and allows for the detection and distinction of pharmacologically and toxicologically active compounds. Diffusion time distribution analysis has the potential to become a general approach to monitor physical properties of biochemical networks in living cells.