WG1: High-resolution AFM of biological systems from molecule to cells

 State of the art

The atomic force microscope (AFM) has become a powerful tool for the structural investigation of biological samples. Invaluable trump, compared to other techniques employed the AFM works under native-like conditions: experiments are performed in physiological buffer at room temperature and under normal pressure. Topographs of biomolecules can be acquired at a lateral resolution of ~10Å and a vertical resolution of ~1Å at an extraordinary signal-to-noise ratio.

 Background and Scientific Program

 Imaging techniques in medicine are important for our understanding of pathologies and potential development of cures. It is now clear that many pathologies are based on molecular disorders – therefore techniques capable to image at a resolution sufficient to observe single molecules and better must be developed. AFM as a medical nano-imaging tool is able to image individual molecules from healthy or pathological tissues.

First, the Working Group 1 (WG1) will improve existing and develop novel sample preparation methods, because it is of major importance to standardize the starting point of scientific and medical investigation approaches (This aspect will be shared with WG2 and WG3).

Second, improved understanding of imaging on the biological objects will also be elaborated, in order to minimize the invasiveness of the investigation. This comprises the evaluation of several technical strategies (such as the development high-sensitivity detectors, non-contact modes, minimal amplitude oscillating imaging modes etc) and adapted conditions (finding the optimal imaging condition and/or the optimal condition for the nativeness of the biological sample, or the most intelligent tradeoff between both).

Third, in relation to the prior point, instrumentation will be improved, with focus on pushing towards an “easy-to-handle AFM”. This will bring the AFM to a wider use, and aims to bring AFM into the hands of non-physicist users, particularly actors in medical research (These aspects will be elaborated in tight relation with WG5).

Fourth, WG1 will improve instrumentation: More sensitive force control, novel imaging modes, faster scanning for the visualization of dynamic processes (video-speed AFM) will be developed.