[Zurück]

E. Sevcsik:
"Micro‐ and nanostructured biointerfaces for cell interaction";
Vortrag: Habilitandenseminar der Fakultät Physik, TU Wien; 14.10.2021.

Recreating biological phenomena in model systems with defined components and properties has
proven to be a powerful tool for dissecting molecular mechanisms. My research is dedicated to the
development of such model systems that allow the reconstitution, observation and physical
manipulation of cellular processes down to the single molecule level. In particular, I apply micro‐ and
nanostructured biointerfaces to gain a quantitative and mechanistic understanding of plasma
membrane organization and associated cellular signaling processes. In this talk, I will focus on our
recent efforts to study the nanoscale organization of ligands and receptors in cell‐cell contacts, which
is critical for cellular communication yet inherently challenging to investigate. For this, we have
devised a biomimetic interface based on DNA origami nanostructures which allows the experimenter
to adjust protein distances with nanometer precision as a means to enhance or disturb receptor
signaling (1, 2). At the same time, the biointerface is fully responsive to dynamic receptor
rearrangements on the cell surface upon ligand engagement as they typically occur in immunity,
neuro‐ and cancer biology. Applying this biointerface to interrogate the spatial requirements of T‐cell
antigen recognition, we could identify the smallest signaling‐competent receptor unit as two stably
ligated T‐cell receptors (TCRs) within a distance of 20 nanometers. We propose that such signalingcompetent
TCR units evolve via parallel binding of closely spaced high‐affinity ligands or via serial,
rapid and short‐lived engagement by a single physiological pMHC ligand.
1. J. Hellmeier, et al., DNA origami demonstrate the unique stimulatory power of single pMHCs as Tcell
antigens. Proc. Natl. Acad. Sci. U. S. A. 118, e2016857118 (2021).
2. J. Hellmeier, et al., Strategies for the site‐specific decoration of DNA origami nanostructures with
functionally intact proteins. ACS Nano 15, 15057-15068 (2021).