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Dr B. Plochberger

Current Research Interest

 Biology demands a broad spectrum of measurement techniques. Most of them were primarily designed for application to non-biologic materials. However, these techniques often do not offer information that is specific enough. I developed instrumentation for the nanoscopic delivery of substances to living biological cells, and the simultaneous optical detection of cargo transfer. Fluorescence microscopy at the single molecule level allows observation of proteins, lipids, and DNA-molecules in their native enviroment – the living cell – as they perform their endogenous function. In contrast to noninvasive optical microscopy, atomic force microscopy (AFM) has advanced (or evolved?) advanced into a routine tool for the controlled manipulation and stimulation of single biomolecules, the characterization of the molecular recognition processes. Combining single molecule force and fluorescence microscopy thus provides the intriguing perspective for a nanoscopic “touch and watch” experiment, by triggering the biosystem via the AFM and following the response in time via fluorescence microscopy. By utilizing the AFM tip as a nanopipette, a single bioparticle can be delivered in a controlled way to its receptor directly in the cellular plasma membrane. Here, I realised this idea to measure the delivery of single fluorescently labeled lipid molecules into a biomembrane (out of a loaded HDL particle) mounted onto the AFM tip. In particular, the transfer of fluorescently labeled lipids, functioning as the receptor for selective uptake was of major interest.

 The combined atomic force and fluorescence microscope was designed for studying efflux of cholesterol from HDL particles, but has proved far more versatile: I expect such approaches to become enabling methods for future nanobioscience. Besides characterization of the transfer of single lipids out of a HDL particle, the combined system can be used to study further interaction between various receptors and ligands with several affinities and specificities. However, using this setup for T-cell activation may prove far more valuable. In particular, T-cells react extremely sensitively to their environment, which hampers investigations by usual methods. Moreover, it seems that tiny membrane structures are involved, whose existence and nature are disputed due to the lack of appropriate techniques. I believe that the combined setup provides a unique opportunity to gain physical insights into T-cell immunology and could be extended to other prospective scientific problems.


biophysics/birgit_plotchberger/index.txt · Last modified: 2012-06-20 16:18 by Elena Parkinson