Flaw tolerance of nuclear intermediate filament lamina under extreme mechanical deformation.

The nuclear lamina, composed of intermediate filaments, is a structural protein meshwork at the nuclear membrane that protects genetic material and regulates gene expression. Here we uncover the physical basis of the material design of nuclear lamina that enables it to withstand extreme mechanical deformation of >100% strain despite the presence of structural defects. Through a simple in silico model we demonstrate that this is due to nanoscale mechanisms including protein unfolding, alpha-to-beta transition, and sliding, resulting in a characteristic nonlinear force-extension curve.

Self-folding and aggregation of amyloid nanofibrils.

Amyloids are highly organized protein filaments, rich in β-sheet secondary structures that self-assemble to form dense plaques in brain tissues affected by severe neurodegenerative disorders (e.g. Alzheimer's Disease).

Failure of Aβ(1-40) amyloid fibrils under tensile loading.

Amyloid fibrils and plaques are detected in the brain tissue of patients affected by Alzheimer's disease, but have also been found as part of normal physiological processes such as bacterial adhesion. Due to their highly organized structures, amyloid proteins have also been used for the development of nanomaterials, for a variety of applications including biomaterials for tissue engineering, nanolectronics, or optical devices. Past research on amyloid fibrils resulted in advances in identifying their mechanical properties, revealing a remarkable stiffness.

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen.

Collagen is a key constituent in structural materials found in biology, including bone, tendon, skin and blood vessels. Here we report a first molecular level model of an entire overlap region of a C-terminal cross-linked type I collagen assembly and carry out a nanomechanical characterization based on large-scale molecular dynamics simulation in explicit water solvent. Our results show that the deformation mechanism and strength of the structure are greatly affected by the presence of the cross-link, and by the specific loading condition of how the stretching is applied.

Multiscale aspects of mechanical properties of biological materials.

Multiscale aspects of mechanical properties of biological materials have developed into an emerging area of research with impact in a broad range of disciplines ranging from medicine to materials science, defining a biomateriomics approach that facilitates a new paradigm in understanding the interplay of structure and function. Mechanical properties of biological materials are critical for virtually all physiological processes and cover all the scales, from the molecular to the macroscale, and provide access to mechanistic understanding and engineering design of novel tools for disease diagnosis, disease treatment and biomaterials development or for the transfer of biologically inspired materials and structures. The integrated use of simulation and experiment can address key challenges in this field and will result in new tools for the analysis and synthesis of complex materials.

Cooperative deformation of hydrogen bonds in beta-strands and beta-sheet nanocrystals.

Beta-sheet protein domains are stabilized by weak hydrogen bonds, yet materials such as silk--whose ultimate tensile strength is controlled primarily by this secondary structure--can exceed the ultimate tensile strength of steel. Earlier work has suggested that this is because hydrogen bonds deform cooperatively within small protein domains to reach the maximum strength. Here we study the atomistic mechanism of this concerted deformation mechanism by applying an elastic structural model, used to solve the deformation field of the chemical bonds in beta-sheet nanostructures under stretching and thereby identify the number of hydrogen bonds that deform cooperatively.

Hierarchical simulations for the design of supertough nanofibers inspired by spider silk.

Biological materials such as spider silk display hierarchical structures, from nano to macro, effectively linking nanoscale constituents to larger-scale functional material properties. Here, we develop a model that is capable of determining the strength and toughness of elastic-plastic composites from the properties, percentages, and arrangement of its constituents, and of estimating the corresponding dissipated energy during damage progression, in crack-opening control. Specifically, we adopt a fiber bundle model approach with a hierarchical multiscale self-similar procedure which enables to span various orders of magnitude in size and to explicitly take into account the hierarchical topology of natural materials.

Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up.

Collagen constitutes one-third of the human proteome, providing mechanical stability, elasticity, and strength to organisms and is the prime construction material in biology. Collagen is also the dominating material in the extracellular matrix and its stiffness controls cell differentiation, growth, and pathology. However, the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility, and nonlinear mechanical response at large deformation, remains unknown.

Atomistic study of crack-tip cleavage to dislocation emission transition in silicon single crystals.

At low temperatures silicon is a brittle material that shatters catastrophically, whereas at elevated temperatures, the behavior of silicon changes drastically over a narrow temperature range and suddenly becomes ductile. This brittle-to-ductile transition has been observed in experimental studies, yet its fundamental mechanisms remain unknown. Here we report an atomistic-level study of a fundamental event in this transition, the change from brittle cleavage fracture to dislocation emission at crack tips, using the first principles based reactive force field.

Molecular dynamics simulation of the α-helix to β-sheet transition in coiled protein filaments: evidence for a critical filament length scale.

The alpha-helix to beta-sheet transition (α-β transition) is a universal deformation mechanism in alpha-helix rich protein materials such as wool, hair, hoof, and cellular proteins. Through a combination of molecular and theoretical modeling, we examine the behavior of alpha-helical coiled-coil proteins with varying lengths under stretch. We find that the occurrence of the α-β transition is controlled by the length of constituting alpha-helical proteins.

Mechanical energy transfer and dissipation in fibrous beta-sheet-rich proteins.

Mechanical properties of structural protein materials are crucial for our understanding of biological processes and disease states. Through utilization of molecular simulation based on stress wave tracking, we investigate mechanical energy transfer processes in fibrous beta-sheet-rich proteins that consist of highly ordered hydrogen bond (H-bond) networks. By investigating four model proteins including two morphologies of amyloids, beta solenoids, and silk beta-sheet nanocrystals, we find that all beta-sheet-rich protein fibrils provide outstanding elastic moduli, where the silk nanocrystal reaches the highest value of ≈40 GPa.

Plasticity of intermediate filament subunits.

Intermediate filaments (IFs) assembled in vitro from recombinantly expressed proteins have a diameter of 8-12 nm and can reach several micrometers in length. IFs assemble from a soluble pool of subunits, tetramers in the case of vimentin. Upon salt addition, the subunits form first unit length filaments (ULFs) within seconds and then assembly proceeds further by end-to-end fusion of ULFs and short filaments.

Mutations alter the geometry and mechanical properties of Alzheimer's Aβ(1-40) amyloid fibrils.

The identification of more efficient therapies for defeating severe degenerative diseases like Alzheimer's is a major goal of drug discovery research. Realizing this ambitious goal will likely require a series of molecular insights that shed light on the fundamental mechanisms that drive the formation, growth, stability, and toxicity of Aβ(1-40) amyloid fibrils, one of the most abundant species found in affected brain tissues and potentially a major player in the progression of Alzheimer's disease. Amyloid fibrils feature a highly ordered and dense network of hydrogen bonds, a universal feature of all amyloid structures, which is realized by a highly regular stacking of small β-units that are each stabilized by an intrapeptide salt bridge.

How protein materials balance strength, robustness, and adaptability.

Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro.

Geometry controls conformation of graphene sheets: membranes, ribbons, and scrolls.

Graphene features a two-dimensional structure, where applications from electronic building blocks to reinforced composites are emerging, enabled through the utilization of its intriguing electrical, mechanical, and thermal properties. These properties are controlled by the structural makeup of graphene, which is known to display multiple morphologies that change under thermal fluctuations and variations of its geometry. However, as of now, a systematic understanding of the relationship between the conformation of graphene and its geometry remains unknown, preventing rational bottom-up design of materials, structures, and devices.

In silico assembly and nanomechanical characterization of carbon nanotube buckypaper.

Carbon nanotube sheets or films, also known as 'buckypaper', have been proposed for use in actuating, structural and filtration systems, based in part on their unique and robust mechanical properties. Computational modeling of such a fibrous nanostructure is hindered by both the random arrangement of the constituent elements as well as the time- and length-scales accessible to atomistic level molecular dynamics modeling. Here we present a novel in silico assembly procedure based on a coarse-grain model of carbon nanotubes, used to attain a representative mesoscopic buckypaper model that circumvents the need for probabilistic approaches.

Nanostructure and molecular mechanics of spider dragline silk protein assemblies.

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis.

Molecular and nanostructural mechanisms of deformation, strength and toughness of spider silk fibrils.

Spider dragline silk is one of the strongest, most extensible and toughest biological materials known, exceeding the properties of many engineered materials including steel. Silk features a hierarchical architecture where highly organized, densely H-bonded beta-sheet nanocrystals are arranged within a semiamorphous protein matrix consisting of 3(1)-helices and beta-turn protein structures. By using a bottom-up molecular-based approach, here we develop the first spider silk mesoscale model, bridging the scales from Angstroms to tens to potentially hundreds of nanometers.

Alzheimer's abeta(1-40) amyloid fibrils feature size-dependent mechanical properties.

Amyloid fibrils are highly ordered protein aggregates that are associated with several pathological processes, including prion propagation and Alzheimer's disease. A key issue in amyloid science is the need to understand the mechanical properties of amyloid fibrils and fibers to quantify biomechanical interactions with surrounding tissues, and to identify mechanobiological mechanisms associated with changes of material properties as amyloid fibrils grow from nanoscale to microscale structures. Here we report a series of computational studies in which atomistic simulation, elastic network modeling, and finite element simulation are utilized to elucidate the mechanical properties of Alzheimer's Abeta(1-40) amyloid fibrils as a function of the length of the protein filament for both twofold and threefold symmetric amyloid fibrils.

Tearing graphene sheets from adhesive substrates produces tapered nanoribbons.

Graphene is a truly two-dimensional atomic crystal with exceptional electronic and mechanical properties. Whereas conventional bulk and thin-film materials have been studied extensively, the key mechanical properties of graphene, such as tearing and cracking, remain unknown, partly due to its two-dimensional nature and ultimate single-atom-layer thickness, which result in the breakdown of conventional material models. By combining first-principles ReaxFF molecular dynamics and experimental studies, a bottom-up investigation of the tearing of graphene sheets from adhesive substrates is reported, including the discovery of the formation of tapered graphene nanoribbons.

Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models.

Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al.

Nanoconfinement controls stiffness, strength and mechanical toughness of beta-sheet crystals in silk.

Silk features exceptional mechanical properties such as high tensile strength and great extensibility, making it one of the toughest materials known. The exceptional strength of silkworm and spider silks, exceeding that of steel, arises from beta-sheet nanocrystals that universally consist of highly conserved poly-(Gly-Ala) and poly-Ala domains. This is counterintuitive because the key molecular interactions in beta-sheet nanocrystals are hydrogen bonds, one of the weakest chemical bonds known.

Intermediate filament-deficient cells are mechanically softer at large deformation: a multi-scale simulation study.

The cell's cytoskeleton, providing cells with structure and shape, consists of different structural proteins, including microtubules, actin microfilaments and intermediate filaments. It has been suggested that intermediate filaments play a crucial role in providing mechanical stability to cells. By utilizing a simple coarse-grained computational model of the intermediate filament network in eukaryotic cells, we show here that intermediate filaments play a significant role in the cell mechanical behavior at large deformation, and reveal mechanistic insight into cell deformation under varying intermediate filament densities.