Cellular-based AFM studies on Nanomedicine, Nanodiagnosis and Nanosensing.

AFM has become a powerful biomedical research instrument for the visualization, probing and manipulation of biological systems from living cells down to single molecules. Importantly, AFM measurements can be carried out in buffer solution under physiological conditions without labelling procedures, which is fundamental to study the structure and function of biological objects under medical relevance.

One main direction in AFM in Nanomedicine focuses on the mechanical stiffness probing of living cells to elaborate their physiological function state and its dependency from the buffered environment, like the concentrations of Na+ and K+. These observations give for the first time insights into functional mechanisms that regulate blood pressure via the stiffness of cells that coat the inner walls of human blood vessels. Another important line of research demonstrated that AFM nanomechanical probing can identify cancerous cells via their stiffness and discriminate between the metastatic cancer and benign cells. AFM studies correlated well with immunohistochemical testing currently used for detecting cancer. It was found that different cancer types displayed a common stiffness.

In recent years the powerful combination of AFM with optical/fluorescence microscopy has opened new avenues for NanoMed&Bio, most importantly the possibility to correlate optical and AFM information. Using the combined AFM-fluorescence technique for the first time simultaneously the electrical plasma membrane potential and mechanical stiffness in a living cell have been monitored.

The described method is applicable for any fluorophore, which opens new perspectives in biomedical research. Further important combinations of AFM with other techniques include Raman spectroscopy (TERS, tip enhanced Raman) enabling nanoscale chemical identification promising fundamental breakthroughs for nanosensing and early state diagnosis. Complementary to AFM instrumentation, research on sensing platforms for diagnosis and systems for controlled drug release are of fundamental importance for the development of AFM based Nanomedicine. This includes surface engineering for controlled cell and protein adsorption and the use of vesicles and polymersomes as drug carriers and nanoreactors.