Research Training Group 2154 - Materials for Brain

Sandra Sindt

Investigation of cellular mechanotransduction using AFM-based force spectroscopy

In nature, cells experience multiple mechanical cues that can affect their behavior. The process in which cells feel and respond to these mechanical cues is called mechanotransduction. However, the underlying mechanisms are not completely understood yet but most probable a combination of protein unfolding and mechanosensitive ion channels are responsible for mechanotransduction.
Due to the diverse possibilities to manipulate cells and their behavior, the understanding of mechanotransduction offers a great new strategy for medical applications of biomaterials, especially in the brain.
In my PhD project, I use different approaches to understand basic principles of mechanotransduction. Mainly, I investigate how mechanical properties of the cell surrounding (e.g. through a material) or external forces applied to cells (e.g. through an AFM-cantilever) affect cells.
An important aspect to manipulate cells in a precise and controlled way is the determination of mechanical properties of the used materials. For this purpose, I use Atomic Force Microscopy (AFM)-based microindentation where a small bead is attached to the cantilever and pressed on the material. Together with a colleague, I developed a controlled, reliable and automatic way to measure and analyze huge amounts of data sets recorded with AFM.
For the passive manipulation of cells and their behavior, I use for example different thick hydrogels on stiff glass substrates. Cells can feel the stiff underlying substrate up to a certain thickness threshold and respond with changes of shape or adhesion area.
However, the active manipulation or stimulation of cell behavior can also be of great importance for medical applications. For this, I use AFM-based force spectroscopy to induce different mechanical stimulations. This offers the possibility to measure the detachment force and work as a function of different mechanical stimuli. To understand further aspects of mechanotransduction, we work with our cooperation partner at the University of New South Wales, Sydney, Australia, to investigate the role of mechanosensitive ion channels.