Atomic Force Microscope

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 492390964

The detailed investigation of the mechanical properties relevant for biological cell and tissues function has greatly enhanced our understanding of the complex regulation relevant in both, healthy cell function but also in several pathological situations. To gain a full picture of cell and tissue mechanics, our team has its focus on a detailed quantification of the viscoelastic properties and the force generation within cells and at the cell-cell and cell-substrate interface. Due to my recent move from Münster to Göttingen, I need to purchase an AFM to establish such projects in the new host institute. As modern biophysical questions require detailed knowledge about the biological systems studied, we need to simultaneously acquire the cell mechanical measurements while gaining structural and dynamical information about the system investigated via fluorescent microscopy. Since we are interested in biological systems with a relevant 3D extension, we will attach the AFM to a spinning disk microscope that is present in the institute. Although the vibration of the spinning disk might reduce the spatial resolution of the AFM, our application in tissue mechanics is not affected. The unique combination of 3D spinning disk microscopy and AFM mechanics, as well as AFM based adhesion measurements will allow us to directly describe the interactions between intracellular and cortical mechanical properties in single cells, but also in reconstituted tissue and organoids. Beside interphase cells, we will also study mitotic cells, and oocytes undergoing miosis. In a further direction we will investigate the viscoelastic properties of tissue, such as cancer spheroids, or small organoids such as lumen forming epithelial acini. The mechanical information obtained from the AFM measurements will be combined with tissue flow measurements obtained from light sheet microscopy, to directly describe tissue dynamics by a hydrodynamical approach. Here not only the viscoelastic properties are relevant, we also need to determine the cell-cell adhesion forces used by the cells to integrate into the tissue. In another direction we investigate the mechanical homeostasis of muscle tissue, where we see significant differences in the mechanical homeostasis of reconstituted muscle tissue from healthy subjects and patients suffering for a mutation in the dystrophin protein, leading to severe muscular dystrophies. Besides these main directions, the new microscope will be used in local cooperation to study the mechanical effect in cell-cell junctions (Andreas Janshoff) and the influence of intermediate filaments on the cortical stiffness (Sarah Köster). In a further direction we aim at imaging structures formed by DNA-origami (Jörg Enderlein). For this project the Spinning-Disk component will be turned off to avoid additional vibrations.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Rasterkraftmikroskop
• Instrumentation Group: 5091 Rasterkraft-Mikroskope
• Applicant Institution: Georg-August-Universität Göttingen
• Leader: Professor Dr. Timo Betz