Agonist mobility on supported lipid bilayers affects Fas mediated death response

• Published in: FEBS letters 2015-11, Vol.589 (23), p.3527-3533
• Main Authors: Sánchez, M. Florencia, Levi, Valeria, Weidemann, Thomas, Carrer, Dolores C.
• Format: Article
• Language: English
• Subjects: Apoptosis; Fas receptor; fas Receptor - agonists; fas Receptor - metabolism; Fluorescence correlation spectroscopy; Functionalized surface; HEK293 Cells; Humans; Lipid Bilayers - metabolism; Membrane Fluidity; Movement; Supported lipid bilayer
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.10.009

•Fas receptor mediated apoptosis is important for many physiological and pathological situations.•The natural ligand of Fas is FasL, a transmembrane protein present in natural killer lymphocytes.•The role of a membrane embedded ligand mobility in Fas mediated death is not well understood.•We stimulated apoptosis on supported bilayers, and quantified ligand mobility by z-scan FCS.•The apoptotic response correlates with increased lateral mobility of the agonist in the membrane. Extrinsic apoptosis is initiated by recognition and clustering of the single-pass transmembrane proteins Fas ligand and Fas expressed at the surface of closely apposed lymphocytes and target cells, respectively. Since Fas-mediated death response was mainly studied with soluble antibodies, the mobility constraints for receptor activation by a membrane embedded agonist is not well understood. We explored this influence by stimulating apoptosis on functionalized supported lipid bilayers, where we quantified agonist mobility by z-scan fluorescence correlation spectroscopy. Using different lipid compositions, we show that the apoptotic response correlates with increased lateral mobility of the agonist in the lipid bilayer.