A coarse-grained mechanical model for folding and unfolding of tropoelastin with possible mutations

We propose a simple general framework to predict folding, native states, energy barriers, protein unfolding, as well as mutation induced diseases and other protein structural analyses. The model should not be considered as an alternative to classical approaches (Molecular Dynamics or Monte Carlo) because it neglects low scale details and rather focuses on global features of proteins and structural information. We aim at the description of phenomena that are out of the range of classical molecular modeling approaches due to the large computational cost: multimolecular interactions, cyclic behavior under variable external interactions, and similar. To demonstrate the effectiveness of the approach in a real case, we focus on the folding and unfolding behavior of tropoelastin and its mutations. Specifically, we derive a discrete mechanical model whose structure is deduced based on a coarse graining approach that allows us to group the amino acids sequence in a smaller number of èquivalent’ masses. Nearest neighbor energy terms are then introduced to reproduce the interaction of such amino acid groups. Next, non-nearest neighbor energy terms inter and intra functional blocks are phenomenologically added in the form of Morse potentials. As we show, the resulting system reproduces important properties of the folding-unfolding mechanical response, including the, monotonic and cyclic force-elongation behavior representing a physiologically important information for elastin. The comparison with the experimental behavior of mutated tropoelastin confirms the predictivity of the model

Solving the Controversy on the Wetting Transparency of Graphene

Since its discovery, the wetting transparency of graphene, the transmission of the substrate wetting property over graphene coating, has gained significant attention due to its versatility for potential applications. Yet, there have been debates on the interpretation and validity of the wetting transparency. Here, we present a theory taking two previously disregarded factors into account and elucidate the origin of the partial wetting transparency. We show that the liquid bulk modulus is crucial to accurately calculate the van der Waals interactions between the liquid and the surface, and that various wetting states on rough surfaces must be considered to understand a wide range of contact angle measurements that cannot be fitted with a theory considering the flat surface. In addition, we reveal that the wetting characteristic of the substrate almost vanishes when covered by any coating as thick as graphene double layers. Our findings reveal a more complete picture of the wetting transparency of graphene as well as other atomically thin coatings, and can be applied to study various surface engineering problems requiring wettability-tuning.Korea (South). Ministry of Science, ICT & Future Planning (National Research Foundation of Korea. Basic Science Research Program (2013R1A1A010091))United States. Dept. of Defense (Presidential Early Career Award for Scientists and Engineers

Evidence of the Most Stretchable Egg Sac Silk Stalk, of the European Spider of the Year Meta menardi

Spider silks display generally strong mechanical properties, even if differences between species and within the same species can be observed. While many different types of silks have been tested, the mechanical properties of stalks of silk taken from the egg sac of the cave spider Meta menardi have not yet been analyzed. Meta menardi has recently been chosen as the “European spider of the year 2012”, from the European Society of Arachnology. Here we report a study where silk stalks were collected directly from several caves in the north-west of Italy. Field emission scanning electron microscope (FESEM) images showed that stalks are made up of a large number of threads, each of them with diameter of 6.03±0.58 µm. The stalks were strained at the constant rate of 2 mm/min, using a tensile testing machine. The observed maximum stress, strain and toughness modulus, defined as the area under the stress-strain curve, are 0.64 GPa, 751% and 130.7 MJ/m(3), respectively. To the best of our knowledge, such an observed huge elongation has never been reported for egg sac silk stalks and suggests a huge unrolling microscopic mechanism of the macroscopic stalk that, as a continuation of the protective egg sac, is expected to be composed by fibres very densely and randomly packed. The Weibull statistics was used to analyze the results from mechanical testing, and an average value of Weibull modulus (m) is deduced to be in the range of 1.5–1.8 with a Weibull scale parameter (σ (0)) in the range of 0.33–0.41 GPa, showing a high coefficient of correlation (R(2) = 0.97)

Intracellular pathways involved in bone regeneration triggered by recombinant silk-silica chimeras

Biomineralization at the organic-inorganic interface is critical to many biology material functions in vitro and in vivo. Recombinant silk-silica fusion peptides are organic-inorganic hybrid material systems that can be effectively used to study and control biologically-mediated mineralization due to the genetic basis of sequence control. However, to date, the mechanisms by which these functionalized silk-silica proteins trigger the differentiation of human mesenchymal stem cells (hMSCs) to osteoblasts remain unknown. To address this challenge, we analyzed silk-silica surfaces for silica-hMSC receptor binding and activation, and the intracellular pathways involved in the induction of osteogenesis on these bioengineered biomaterials. The induction of gene expression of αVβ3 integrin, all three Mitogen-activated Protein Kinsases (MAPKs) as well as c-Jun, Runt-related Transcription Factor 2 (Runx2) and osteoblast marker genes was demonstrated upon growth of the hMSCs on the silk-silica materials. This induction of key markers of osteogenesis correlated with the content of silica on the materials. Moreover, computational simulations were performed for silk/silica-integrin binding which showed activation of αVβ3 integrin in contact with silica. This integrated computational and experimental approach provides insight into interactions that regulate osteogenesis towards more efficient biomaterial designs

Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling.

Molecular alteration in type I collagen, i.e., substituting the α2 chain with α1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (OI), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual-frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease

Structural hierarchies define toughness and defect-tolerance despite simple and mechanically inferior brittle building blocks

Mineralized biological materials such as bone, sea sponges or diatoms provide load-bearing and armor functions and universally feature structural hierarchies from nano to macro. Here we report a systematic investigation of the effect of hierarchical structures on toughness and defect-tolerance based on a single and mechanically inferior brittle base material, silica, using a bottom-up approach rooted in atomistic modeling. Our analysis reveals drastic changes in the material crack-propagation resistance (R-curve) solely due to the introduction of hierarchical structures that also result in a vastly increased toughness and defect-tolerance, enabling stable crack propagation over an extensive range of crack sizes. Over a range of up to four hierarchy levels, we find an exponential increase in the defect-tolerance approaching hundred micrometers without introducing additional mechanisms or materials. This presents a significant departure from the defect-tolerance of the base material, silica, which is brittle and highly sensitive even to extremely small nanometer-scale defects

Nanomaterials: Strenght in numbers

Self-assembly of proteins commonly associated with neurodegenerative diseases can be exploited to make well-ordered and strong functional macroscopic materials

Mechanics of fragmentation of crocodile skin and other thin films

Fragmentation of thin layers of materials is mediated by a network of cracks on its surface. It is commonly seen in dehydrated paintings or asphalt pavements and even in graphene or other two-dimensional materials, but is also observed in the characteristic polygonal pattern on a crocodile’s head. Here, we build a simple mechanical model of a thin film and investigate the generation and development of fragmentation patterns as the material is exposed to various modes of deformation. We find that the characteristic size of fragmentation, defined by the mean diameter of polygons, is strictly governed by mechanical properties of the film material. Our result demonstrates that skin fragmentation on the head of crocodiles is dominated by that it features a small ratio between the fracture energy and Young’s modulus, and the patterns agree well with experimental observations. Understanding this mechanics-driven process could be applied to improve the lifetime and reliability of thin film coatings by mimicking crocodile skin

Phase Transitions and Their Interaction with Dislocations in Silicon

In this paper, phase transformations (PTs) in silicon were investigated through molecular dynamics (MD) using Tersoff potential. In the first step, simulations of PTs in single crystal silicon under various stress-controlled loading were carried out. Results shows that all instability points under various stress states are described by criteria, which are linear in the space of normal stresses. There is a region in the stress space in which conditions for direct and reverse PTs coincide and a unique homogeneous phase transition (without nucleation) can be realized. Finally, phase transition in bi-crystalline silicon with a dislocation pileup along the grain boundary (GB) was carried out. Results showed that the phase transition pressure first decreases linearly with the number of dislocation pileups and then reaches a plateau with the accumulation of dislocations in the pileup. The maximum reduction of phase transition pressure is 30% compared to that for perfect single crystalline silicon

Category Theoretic Analysis of Hierarchical Protein Materials and Social Networks

Materials in biology span all the scales from Angstroms to meters and typically consist of complex hierarchical assemblies of simple building blocks. Here we describe an application of category theory to describe structural and resulting functional properties of biological protein materials by developing so-called ologs. An olog is like a “concept web” or “semantic network” except that it follows a rigorous mathematical formulation based on category theory. This key difference ensures that an olog is unambiguous, highly adaptable to evolution and change, and suitable for sharing concepts with other olog. We consider simple cases of beta-helical and amyloid-like protein filaments subjected to axial extension and develop an olog representation of their structural and resulting mechanical properties. We also construct a representation of a social network in which people send text-messages to their nearest neighbors and act as a team to perform a task. We show that the olog for the protein and the olog for the social network feature identical category-theoretic representations, and we proceed to precisely explicate the analogy or isomorphism between them. The examples presented here demonstrate that the intrinsic nature of a complex system, which in particular includes a precise relationship between structure and function at different hierarchical levels, can be effectively represented by an olog. This, in turn, allows for comparative studies between disparate materials or fields of application, and results in novel approaches to derive functionality in the design of de novo hierarchical systems. We discuss opportunities and challenges associated with the description of complex biological materials by using ologs as a powerful tool for analysis and design in the context of materiomics, and we present the potential impact of this approach for engineering, life sciences, and medicine.Presidential Early Career Award for Scientists and Engineers (N000141010562)United States. Army Research Office. Multidisciplinary University Research Initiative (W911NF0910541)United States. Office of Naval Research (grant N000141010841)Massachusetts Institute of Technology. Dept. of MathematicsStudienstiftung des deutschen VolkesClark BarwickJacob Luri