Keratin: Structure, mechanical properties, occurrence in biological organisms, and efforts at bioinspiration

A ubiquitous biological material, keratin represents a group of insoluble, usually high-sulfur content and filament-forming proteins, constituting the bulk of epidermal appendages such as hair, nails, claws, turtle scutes, horns, whale baleen, beaks, and feathers. These keratinous materials are formed by cells filled with keratin and are considered 'dead tissues'. Nevertheless, they are among the toughest biological materials, serving as a wide variety of interesting functions, e.g. scales to armor body, horns to combat aggressors, hagfish slime as defense against predators, nails and claws to increase prehension, hair and fur to protect against the environment. The vivid inspiring examples can offer useful solutions to design new structural and functional materials. Keratins can be classified as α- and β-types. Both show a characteristic filament-matrix structure: 7 nm diameter intermediate filaments for α-keratin, and 3 nm diameter filaments for β-keratin. Both are embedded in an amorphous keratin matrix. The molecular unit of intermediate filaments is a coiled-coil heterodimer and that of β-keratin filament is a pleated sheet. The mechanical response of α-keratin has been extensively studied and shows linear Hookean, yield and post-yield regions, and in some cases, a high reversible elastic deformation. Thus, they can be also be considered 'biopolymers'. On the other hand, β-keratin has not been investigated as comprehensively. Keratinous materials are strain-rate sensitive, and the effect of hydration is significant. Keratinous materials exhibit a complex hierarchical structure: polypeptide chains and filament-matrix structures at the nanoscale, organization of keratinized cells into lamellar, tubular-intertubular, fiber or layered structures at the microscale, and solid, compact sheaths over porous core, sandwich or threads at the macroscale. These produce a wide range of mechanical properties: the Young's modulus ranges from 10 MPa in stratum corneum to about 2.5 GPa in feathers, and the tensile strength varies from 2 MPa in stratum corneum to 530 MPa in dry hagfish slime threads. Therefore, they are able to serve various functions including diffusion barrier, buffering external attack, energy-absorption, impact-resistance, piercing opponents, withstanding repeated stress and aerodynamic forces, and resisting buckling and penetration. A fascinating part of the new frontier of materials study is the development of bioinspired materials and designs. A comprehensive understanding of the biochemistry, structure and mechanical properties of keratins and keratinous materials is of great importance for keratin-based bioinspired materials and designs. Current bioinspired efforts including the manufacturing of quill-inspired aluminum composites, animal horn-inspired SiC composites, and feather-inspired interlayered composites are presented and novel avenues for research are discussed. The first inroads into molecular-based biomimicry are being currently made, and it is hoped that this approach will yield novel biopolymers through recombinant DNA and self-assembly. We also identify areas of research where knowledge development is still needed to elucidate structures and deformation/failure mechanisms

Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance.

One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates

Accurate registration of bones from different developmental stages is achieved by matching the cortical cores.

<p>(A) A time chart of calcein and alizarin injection regimes. To cover the entire period effectively, three marginally overlapping regimes were applied. (B) Histological sections from each of the three injection regimes. At E18.5, green-labeled regions are seen around the middle part of the cortical core in both humerus and femur sections, indicating temporally preserved mineral structures. Similar temporal preservation of the cortical core is exhibited during perinatal and early postnatal development. (C) Color-coded statistical maps depicting the fraction of bones that are mineralized at each point in the bone, based on frontal slices of the femur. Clusters are composed of all bones from a single developmental day (top row), pairs (middle row), and triplets (bottom row) of consecutive developmental days. Regions that are highly preserved in population over several days (color-coded red; middle and bottom rows) are located mostly around the middle part of the cortical core. (D) A time series of frontal slices of the femur with the cortical core highlighted in each image with a different color. On the right is an overlay of all cortical core highlights following anatomical matching. The high overlap between segments demonstrates the potential of the cortical core to serve as a reliable salient structure for accurate anatomical matching of embryonic and early postnatal bones. Scale bars: 500 μm in B–D, 25 μm in B insets I and II, and 50 μm in B inset III.</p