Cells as Living Materials : Force Spectroscopic Investigation of Mechanotransduction

Mechanotransduction describes a cellular mechanism of sensing and converting mechanical cues into biochemical signals to regulate cell processes, such as adhesion, migration, proliferation and/or apoptosis. Thus, becoming an ever-growing field of research with high potential for medical applications.

I present a new strategy towards reliable microindentation measurements, which is essential for investigating mechanotransduction using soft substrates. I show a precise, reproducible determination of Young’s moduli through an automatic analysis of indentation data. The algorithm presented detects Young’s moduli in a region without dependence on indentation depth while minimizing the fitting error. This strategy is a step towards a comprehensive study of soft materials on a spatial scale similar to cell interactions. It has broad applicability ranging from fundamental research to developing innovative implants that match the in vivo situation. Also, I present novel approaches for multifaceted cellular manipulation. I show that layer thickness of a soft material fixed to a stiff underlying substrate can be crucial for cell adhesion. These findings are pioneer for new implant designs and advanced application fields. I present two atomic force microscopy-based manipulation systems that allow applying specific mechanical stimuli to single cells and a subsequent correlation to whole cell detachment and single bond strengths. The unique AFM-based shear system presented combines application of shear stimuli and cell detachment measurements, whereas the AFM-based modulation system combines oscillatory pushing and pulling with cell detachment measurements. Both shear and oscillatory forces are essential in our body.

Thus, the strategies presented in this thesis are of significant medical interest allowing an overarching study of mechanotransduction and may pave the way towards smart stimulation devices that allow cell adhesion on demand.

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