Electrophysiological and mechanical activity of cells triggered and traced on the level of single receptor-ligand interactions

• Applicant: Dr. Martin Benoit
• Subject Area: Biophysics
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 90621944

The complexity of signaling pathways calls for several approaches and strategies to deduce the interconnections between the involved molecules and a measured reaction of the cell. In a majority of experiments the signaling receptors are stimulated by soluble ligands. But sometimes even a stimulus on a single receptor results in a strong cellular activity (e.g. a single photon can trigger a whole photoreceptor cell). Approaches that involve patch-clamp are precise in electrical stimulation and successful in tracing the dynamics of signaling processes since most of them include ion channel activity. Neuronal receptors often directly couple to ion channels. Approaches that focus on mechanical activity of cells still are less favored. Here we want to utilize the nano mechanical precision of an AFM to apply a stimulus to certain molecules on a cell and to record the cellular movement as a response to a stimulus combined with single channel recordings by simultaneous patch-clamp. This unique setup records electro-physiological and mechanical reactions of a cell to a given stimulus at high sampling rate and resolution. The interplay of mechanical and electrophysiological reactions of individual angiotensin II peptides interacting with its G-protein coupled receptor pathway and of individual glutamate molecules interacting with its ionotropic receptor are targeted in this approach for the first time.

• DFG Programme: Research Grants