Atomic force microscopy (AFM) is a versatile imaging technique with nanometer resolution that is ideally suited for investigating organic and inorganic nanostructures on solid surfaces. It has proven particularly useful in the study of biological macromolecules such as proteins or DNA where it may provide unique information on molecular structure, conformation and aggregation. We have thus applied AFM to study disease-relevant molecular aggregation and fragmentation mechanisms in vitro. The denaturation and aggregation of peptides and proteins into highly-ordered amyloid nanofibrils plays an important role in the development of so-called misfolding diseases such as Alzheimer's disease, Parkinson's disease, or prion disease. In the physiological environment, amyloid aggregation is affected by the presence of interfaces such as cell membranes. By using a novel type of model surface, we were able to investigate the influence of surface hydrophobicity on the surface-catalyzed aggregation of the islet amyloid polypeptide which is critical for the development of type 2 diabetes mellitus. In addition, we present a new AFM-based strategy for the assessment of DNA damage induced by low-energy electrons and ions which are generated as secondary particles in the interaction of biological matter with ionizing radiation, e.g. in radiation tumor therapy. Here, AFM provides the unique possibility to study the fragmentation of complex DNA structures at the single-molecule level.
Atomic force microscopy (AFM) is a versatile imaging technique with nanometer resolution that is ideally suited for investigating organic and inorganic nanostructures on solid surfaces. It has proven particularly useful in the study of biological macromolecules such as proteins or DNA where it may provide unique information on molecular structure, conformation and aggregation. We have thus applied AFM to study disease-relevant molecular aggregation and fragmentation mechanisms in vitro. The denaturation and aggregation of peptides and proteins into highly-ordered amyloid nanofibrils plays an important role in the development of so-called misfolding diseases such as Alzheimer's disease, Parkinson's disease, or prion disease. In the physiological environment, amyloid aggregation is affected by the presence of interfaces such as cell membranes. By using a novel type of model surface, we were able to investigate the influence of surface hydrophobicity on the surface-catalyzed aggregation of the islet amyloid polypeptide which is critical for the development of type 2 diabetes mellitus. In addition, we present a new AFM-based strategy for the assessment of DNA damage induced by low-energy electrons and ions which are generated as secondary particles in the interaction of biological matter with ionizing radiation, e.g. in radiation tumor therapy. Here, AFM provides the unique possibility to study the fragmentation of complex DNA structures at the single-molecule level.
