Alpha-helical protein networks are self-protective and flaw-tolerant.

Alpha-helix based protein networks as they appear in intermediate filaments in the cell's cytoskeleton and the nuclear membrane robustly withstand large deformation of up to several hundred percent strain, despite the presence of structural imperfections or flaws. This performance is not achieved by most synthetic materials, which typically fail at much smaller deformation and show a great sensitivity to the existence of structural flaws. Here we report a series of molecular dynamics simulations with a simple coarse-grained multi-scale model of alpha-helical protein domains, explaining the structural and mechanistic basis for this observed behavior.

Alpha-helical protein domains unify strength and robustness through hierarchical nanostructures.

Hierarchical nanostructures, ranging through atomistic, molecular and macroscopic scales, represent universal features of biological protein materials. Here we show for the case of alpha-helical (AH) protein domains that this use of molecular hierarchies within the structural arrangement leads to an extended physical dimension in the material design space that resolves the conflict between disparate material properties such as strength and robustness, a limitation faced by many synthetic materials. An optimal combination of redundancies at different hierarchical levels enables superior mechanical performance without additional material use.

A multi-timescale strength model of alpha-helical protein domains.

Here we report a constitutive model that characterizes the strength of an alpha-helical protein domain subjected to tensile deformation, covering more than ten orders of magnitude in timescales. The model elucidates multiple physical mechanisms of failure in dependence on the deformation rate, quantitatively linking atomistic simulation results with experimental strength measurements of alpha-helical protein domains. The model provides a description of the strength of alpha-helices based on fundamental physical parameters such as the H-bond energy and the polypeptide's persistence length, showing that strength is controlled by energetic, nonequilibrium processes at high rates and by thermodynamical, equilibrium processes at low rates.

Nanomechanical strength mechanisms of hierarchical biological materials and tissues.

Biological protein materials (BPMs), intriguing hierarchical structures formed by assembly of chemical building blocks, are crucial for critical functions of life. The structural details of BPMs are fascinating: They represent a combination of universally found motifs such as alpha-helices or beta-sheets with highly adapted protein structures such as cytoskeletal networks or spider silk nanocomposites. BPMs combine properties like strength and robustness, self-healing ability, adaptability, changeability, evolvability and others into multi-functional materials at a level unmatched in synthetic materials.

Muscle dystrophy single point mutation in the 2B segment of lamin A does not affect the mechanical properties at the dimer level.

Lamin intermediate filaments at the inner nuclear membrane play a key role in mechanosensation and gene regulation processes, and further guarantee the mechanical stability of the cell's nucleus. The rod-like dimers are the elementary building blocks within the dense lamina meshwork, mainly consisting of four alpha-helical coiled-coil segments as fundamental building blocks. Several mutations in the 2B segment of the rod domain of lamin A have been linked to the disease muscle dystrophy.

Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of alpha-helical and beta-sheet protein domains.

The fundamental fracture mechanisms of biological protein materials remain largely unknown, in part, because of a lack of understanding of how individual protein building blocks respond to mechanical load. For instance, it remains controversial whether the free energy landscape of the unfolding behavior of proteins consists of multiple, discrete transition states or the location of the transition state changes continuously with the pulling velocity. This lack in understanding has thus far prevented us from developing predictive strength models of protein materials.