The mechanical properties of each of the more than 200 cell types in the human body are perfectly well adapted to their function. The wide variety of viscoelastic profiles, ranging from soft brain cells to stiff cartilage, and the temporal variability in the mechanical stress response as quiescent cells begin to migrate, e.g. during embryogenesis, wound healing, or cancer metastasis, are reflected in a surprisingly small number of molecular building blocks. Three distinct filament systems (actin filaments, microtubules, and intermediate filaments (IFs)) self-organize into a plethora of structural units, collectively referred to as the cytoskeleton. The major molecular players in this remarkable composite material are largely known. However, from a physical point of view, IFs, in particular, are less well understood, despite their importance in health and disease and astonishing mechanical properties, such as extreme extensibility and high flexibility. Moreover, it remains a challenge to characterize and quantify the interactions between the filaments, which play a major role within the composite intracellular network.
In this project our objective was to investigate how the remarkable mechanical properties of IFs are encoded in the molecular interactions of the protein monomers and how they are translated into the mechanical behavior of a whole cell. Thus, our research established a structure-mechanics-function relationship for this important component of the cytoskeleton. The genetic complexity of the IF protein family with 70 members that are expressed in a tissue-specific manner required a strategic approach with well-defined model systems and the combination of in vitro and cellular work. Direct mechanical testing by stress application was performed in a quantitative manner by optical tweezers.
Our work covers different length scales, from molecular interactions, which are investigated by numerical simulations, via single filament mechanics, interactions between filaments and within networks, to cellular mechanics.
