Intermediate Filaments: Structure-Mechanics Crosstalk

Intermediate filaments (IFs) possess unique mechanical properties that distinguish them from actin filaments and microtubules. In particular, they exhibit high flexibility, pronounced extensibility, and complete stability during biochemical extractions from cells and tissues. These characteristics stem from their molecular structure, which is typical of fibrous proteins. A defining feature is the central ~300 amino acid long α-helical segment with a distinct hydrophobic sequence pattern, facilitating the formation of a parallel coiled-coil dimer. Under low ionic strength conditions, two such dimers interact via their basic amino-terminal domains with the acidic coiled-coil domains to form distinct, rod-like tetrameric complexes. Upon addition of salt, the tetramers first assemble laterally into full-width, unit-length filaments, which then anneal longitudinally into micrometer-long filaments with a characteristic, 10-nm diameter. Advanced experimental techniques enable us to measure piconewton forces and micrometer length scales. By combining, for example, optical tweezers or atomic force microscopy with sophisticated data analysis and numeric modeling, we have deepened our understanding of the structure-mechanics relationship in IFs, including their force-extension behavior and the low bending rigidity. These findings enable us to hypothesize about the mechanical roles of these filaments within the living cell and speculate about biomimetic, synthetic materials.