SKM 2023 – wissenschaftliches Programm

Bereiche | Tage | Auswahl | Suche | Aktualisierungen | Downloads | Hilfe

BP: Fachverband Biologische Physik

BP 21: Bioimaging

BP 21.8: Vortrag

Donnerstag, 30. März 2023, 11:45–12:00, BAR Schö

A Minimal Model of CD95 Signal Initiation Revealed by Advanced Molecular-Sensitive Imaging — •Nina Bartels¹, Nicolaas TM van der Voort², Claus AM Seidel², and Cornelia Monzel¹ — ¹Experimental Medical Physics, Heinrich-Heine University, Düsseldorf, Germany — ²Molecular Physical Chemistry, Heinrich-Heine University, Düsseldorf, Germany

The spatio-temporal organization and dynamic interactions of receptors in the plasma membrane are fundamental for our mechanistic understanding of cell signal initiation. A paradigm of a cell signal initiation process is the ligand-induced oligomerization of TNF (tumor necrosis factor) receptor CD95 in the signaling pathway for apoptosis. Here, we scrutinize proposed CD95 oligomerization models in the cell plasma membrane by applying a molecular sensitive imaging toolkit with up to nanometric resolution including time-resolved FRET spectroscopy, confocal Photobleaching Step Analysis, STED microscopy, and FCS. Covering a wide range of parameters, CD95 interactions are probed over the whole dynamic range from µs to hours, molecular to cellular scales, and with particular focus on quantifying molecular concentrations. Our multiscale study reveals a minimal oligomerization model to trigger apoptosis efficiently, where only ∼8-17% CD95 monomers assemble into dimers/trimers after ligand binding. Further, we highlight the importance of combining complementary techniques for a full understanding of transient and potentially localized processes such as a cell signal initiation.

see also https://doi.org/10.1101/2022.11.29.518370