Mechanical and structural properties of K8/K18 and vimentin intermediate filament (IF) networks have been investigated using bulk mechanical rheometry and optical microrheology including diffusing wave spectroscopy and multiple particle tracking. A high elastic modulus G 0 at low protein concentration c, a weak concentration dependency of G 0 (G 0∼c 0.5±0.1) and pronounced strain stiffening are found for these systems even without external crossbridgers. Strong attractive interactions among filaments are required to maintain these characteristic mechanical features, which have also been reported for various other IF networks. Filament assembly, the persistence length of the filaments and the network mesh size remain essentially unaffected when a nonionic surfactant is added, but strain stiffening is completely suppressed, G 0 drops by orders of magnitude and exhibits a scaling G 0∼c 1.9±0.2 in agreement with microrheological measurements and as expected for entangled networks of semi-flexible polymers. Tailless K8Δ/K18ΔT and various other tailless filament networks do not exhibit strain stiffening, but still show high G 0 values. Therefore, two binding sites are proposed to exist in IF networks. A weaker one mediated by hydrophobic amino acid clusters in the central rod prevents stretched filaments between adjacent cross-links from thermal equilibration and thus provides the high G 0 values. Another strong one facilitating strain stiffening is located in the tail domain with its high fraction of hydrophobic amino acid sequences. Strain stiffening is less pronounced for vimentin than for K8/K18 due to electrostatic repulsion forces partly compensating the strong attraction at filament contact points.

Intermediate filaments (IFs) constitute a sophisticated filament system in the cytoplasm of eukaryotes. They form bundles and networks with adapted viscoelastic properties and are strongly interconnected with the other filament types, microfilaments and microtubules. IFs are cell type specific and apart from biochemical functions, they act as mechanical entities to provide stability and resilience to cells and tissues. We review the physical properties of these abundant structural proteins including both in vitro studies and cell experiments. IFs are hierarchical structures and their physical properties seem to a large part be encoded in the very specific architecture of the biopolymers. Thus, we begin our review by presenting the assembly mechanism, followed by the mechanical properties of individual filaments, network and structure formation due to electrostatic interactions, and eventually the mechanics of in vitro and cellular networks. This article is part of a Special Issue entitled: Mechanobiology.

We investigated the rheological properties and the penetration of differently sized carboxylated nanoparticles in pig pulmonary mucus, on different distance and time scales. Nanoparticles were either mechanically mixed into the mucus samples or deposited as an aerosol, the latter resembling a more physiologically relevant delivery scenario. After mechanical dispersion, 500 nm particles were locally trapped; a fraction of carboxylated tracer particles of 100 or 200 nm in diameter could however freely diffuse in these networks over distances of approximately 20 μm. In contrast, after aerosol deposition on top of the mucus layer only particles with a size of 100 nm were able to penetrate into mucus, suggesting the presence of smaller pores at the air-mucus interface compared to within mucus. These findings are relevant to an understanding of the fate of potentially harmful aerosol particles, such as pathogens, pollutants, and other nanomaterials after incidental inhalation, as well as for the design of pulmonary drug delivery systems.

We have investigated intermediate filament networks assembled from the recombinant keratins K8 and K18 in vitro at various protein and MgCl 2 concentrations using mechanical rheometry. Experimental parameters were chosen such that artifacts from sample surface elasticity or wall slip were avoided, and the gap width did not affect network formation. The modulus G 0 depends weakly on the protein concentration (G 0 $ c 0.5 ) and the critical deformation g crit at which non-linear response sets in is concentration independent. These findings can be rationalized assuming that the cross-link density decreases with decreasing protein concentration, while the filament contour length between cross-links remains unchanged. Thus, filaments are more stretched at lower protein concentrations and this increase in conformational energy partly compensates the free energy decrease related to the change in cross-link density. G 0 is independent of the MgCl 2 concentration indicating that the contribution of stretched filaments decreases when the cross-link density increases. Networks rupture when a critical strain is exceeded, but fully recover within 30 minutes. The non-linear network response is characterized by pronounced strain stiffening with increasing shear stress s. Reduced differential modulus K 0 data obtained at different protein or MgCl 2 concentrations collapse onto a master curve. Two scaling regimes K 0 $ s a are observed with a ¼ 1 at intermediate and a ¼ 0.6 at high stresses. These exponents may be rationalized in terms of the glassy wormlike chain model assuming sticky contacts with finite, constant bond strength. Two distinct scaling regimes could also result from the existence of two types of filament contacts with different bond energies or by the compliance of individual filaments.

The first series of planar dimethyl(selenoether)Pt II complexes, [