Many biological materials, such as natural exoskeletons (armor), are known to undergo a variety of energy dissipating mechanisms at multiple length scales due to their hierarchical, composite structures, leading to the amplification of mechanical properties beyond simple rule of mixtures. In this work, we investigate the nanoscale deformation mechanisms of the highly transparent shell of the bivalve, Placuna placenta (Linnaeus 1785). The highly mineralized shell of P. placenta (~99 wt% calcite) is composed of the foliated microstructure, in which elongated diamond-shaped calcitic laths are arranged in a mosaic-like manner. The c-axes of these calcitic laths are tilted by 24.4 ± 3.5° relative to their surface normals as measured from electron backscattered diffraction, resulting in lath surfaces closely resembling the {108} planes of calcite. Using systematic instrumented nanoindentation experiments we show that P. placenta achieves a combination of superior mechanical properties, including enhanced hardness, penetration resistance, more localized and isotropic deformation, and graceful failure, as compared to calcite, its main constitute. Most importantly, P. placenta exhibits enhanced energy absorption and damage tolerance, indicated by its much higher energy dissipation density (P. placenta: 0.290 ± 0.072 nJ/µm3, calcite: 0.034 ± 0.013 nJ/µm3). Detailed electron microscopy studies reveal two primary energy-dissipating mechanisms: deformation twinning surrounding the impact region and nanoscale plasticity through nanograin formation and reorientation, which are intimately related to the crystallographic and structural features of the nano-/micro-scopic architecture of the shell&’s foliated structure. The e-type deformation twinnings in the calcitic laths were observed in three crystallographically equivalent planes of calcite, i.e. (1-18), (018), and (-108). Deformation twinning is known to occur in geologic calcite and is hypothesized to be enhanced in P. placenta by the nanoscale thickness (~300 nm) and surface roughness of the building blocks of the foliated microstructure. The twin boundaries together with the thin (~2 nm) intercrystalline organic interfaces act as barriers to dislocation motion and catastrophic crack propagation, maintaining structural integrity and localizing nanoscopic deformation and damage to a confined region. The two mechanisms work synergistically, increasing the energy dissipation density by almost an order of magnitude relative to calcite.

While micro-FE simulations have become a standard tool in computational biomechanics, the choice of appropriate material properties is still a relevant topic, typically involving empirical grey value-to-elastic modulus relations. We here derive the voxel-specific volume fractions of mineral, collagen, and water, from tissue-independent bilinear relations between mineral and collagen content in extracellular bone tissue (J. Theor. Biol. 287: 115, 2011), and from the measured X-ray attenuation information quantified in terms of grey values. The aforementioned volume fractions enter a micromechanics representation of bone tissue, as to deliver voxel-specific stiffness tensors. In order to check the relevance of this strategy, we convert a micro Computer Tomograph of a mouse femur into a regular Finite Element mesh, apply forces related to the dead load of a standing mouse, and then compare simulation results based on voxel-specific heterogeneous elastic properties to results based on homogeneous elastic properties related to the spatial average over the solid bone matrix compartment, of the X-ray attenuation coefficients. The element-specific strain energy density illustrates that use of homogeneous elastic properties implies overestimation of the organ stiffness. Moreover, the simulation reveals large tensile normal stresses throughout the femur neck, which may explain the mouse femur neck's trabecular morphology being quite different from the human case, where the femur neck bears compressive forces and bending moments.

As a complement to the ample experimental literature on qualitative features of mineralizing bones, we here present mathematically formulated rules behind the bone mineralization process within and outside the collagen fibrils.
More precisely, we check whether the structural evolution of bone tissue during mineralization can be explained by means of fluid-solid phase transitions in the fibrils and the extrafibrillar space, considered as two thermodynamically closed systems: the mass of lost ionic fluid equals the mass of formed solid mineral in each subvolume, while the collagen mass remains unaltered. The mineralization process is accompanied by an increase in mass density, leading to shrinkage of the compartments, which can be quantified through the change in equatorial diffraction spacing at the fibrillar scale. These propositions are checked through experimental evidences, relating bone mass densities to the equatorial diffraction spacings. Therefore, the mass conservation equations are converted into mass density-diffraction relations, in three consecutive steps: First, the tissue shrinkage is evaluated based on universal bone composition rules. Secondly, this relation is downscaled to the extrafibrillar space, based on the constant mineral concentration in the extracollagenous space and the hydration swelling rule for unmineralized tissues. Thirdly, the fibrillar shrinkage is analogously derived and related to the change in diffraction spacing.
Our mathematical approach is strictly validated through comparison between experimental and predicted neutron diffraction spacings. Very low prediction errors underline the relevance of the computed evolutions of the tissue compartment volumes and volume fractions during the mineralization process in different bone tissues.
Corresponding shrinkage and composition rules are deemed beneficial for further progress in bone materials science and biomedical engineering.

Man-made nanobiocomposites offer promising mechanical properties that can surpass both natural and engineered materials by blending the best properties of biomolecules with polymers. Natural building blocks such as cellulose nanocrystals of can be effectively utilized in polymer composites due their versatility in size, shape, and surface chemistry. Cellulose molecules contain large numbers of hydroxyl side groups, allowing for a high axial modulus, greater than that of even Kevlar, while maintaining a low density and an easily functionalized surface. However, the impact of the size and surface properties of cellulose on the interfacial mechanics of polymers and all-cellulose composites remain to be fully understood.
To address this issue, here we use a molecular dynamics approach to determine the binding energy landscape between two CNC surfaces and between a CNC surface and polymer matrix, so as to predict the failure mechanism of the composite. Furthermore, we modulate the size of the CNC giving further insight into the mechanics governing the size-dependence of the interfacial interaction. We demonstrate the potential of our methodology in helping to design optimal shape and size of the CNC to achieve the desired composite behavior, and correlate our finding with composites found in biological systems.

Traumatic brain injury is a major public health issue, both in the civilian world and in the military one. In order to expand on potential injury mechanisms to the brain, a micromechanical representation of the gray matter is developed. The gray matter contains a large amount of capillaries that supply the necessary oxygen required for maintaining healthy cell and brain function. Even short duration disruption of the oxygen supply can lead to death and damage of neuronal cells present. It has been shown that shearing forces present within blood flow around obstructions can lead to activation and aggregation of the platelets, which can lead to thrombus formation. While current macro-scale models of the brain can include representation of the larger vasculature present, it is too computationally intensive to model all of the microvasculature present. However, macro-scale models can be used to determine the forces present at various points within the brain, and these forces can be used within a micro-scale model to determine the forces at the platelet level. A micromechanical computational model is developed with gray matter, capillaries, and blood, which is composed of plasma, red blood cells, and platelets. This model combines both fluids and viscoelastic solid materials, so it becomes necessary to use a combined Langrangian-Eulerian finite element approach is to determine the interaction of the platelets with the plasma present within the blood, and to determine whether damage criteria are met for potential shear-induced platelet activation. In addition, this micromechanical model can also be used to develop bottom-up constitutive models for the gray matter, based on the individual materials, in order to better model the macro-scale response of the brain.

Piezoelectricity in collagen is a fundamental phenomenon which has been linked with the ability of bone to remodel. The complex system response of bone to a wide variety of forces (compressive, shearing, axial, etc.) is poorly understood. The high degree of structural organization in collagen and the anisotropy of the piezoelectric properties of collagen make it uniquely suited as a means for cells to locally differentiate between varying stresses. Macroscopic piezoelectricity measurements made to date, however, represent a combination of numerous collagen fibrils with differing orientations. Therefore, it is difficult to obtain accurate piezoelectric coefficient values in the case of collagen. To date, the piezoelectric tensor of a single collagen fibril is not known. However, with the advent of new tools like piezoresponse force microscopy (PFM), it is now possible to probe piezoelectricity on the nanoscale. In order to investigate the dependence of piezoelectricity on the orientation of collagen, tendon, a connective tissue composed of highly aligned collagen fibrils, was studied. Rat tail tendon was embedded in epoxy and cut at angles 0, 45 and 90 degrees relative to the tendon axis. By relating the crystal and laboratory coordinate system and assuming the crystal structure of collagen to be the hexagonal C6 group, it was possible to directly measure the d33 and d15 piezoelectric coefficients via PFM and to mathematically deduce the remaining nonzero (d14 and d31) piezoelectric coefficients in order to reconstruct collagens tensor at the fibrillar scale.

The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at near-millimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone&’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging, irradiation and disease can lead to a markedly increased fracture risk, which is often associated with a loss in bone mass (bone quantity). However, these factors can also significantly degrade the fracture resistance (bone quality) over multiple length-scales.
Using a suite of materials science characterization techniques, including in situ small -angle x-ray scattering/wide-angle x-ray diffraction (SAXS/WAXD) to characterize sub-micron to nanoscale structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron- to macro-scales, we show how age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity by fibrillar sliding at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking. Analogous mechanisms for the embrittlement of bone due to x-ray irradiation are also presented, together with a discussion of the effect of bone diseases on bone strength and toughness, specifically due to osteogenesis imperfecta and vitamin-D deficiency.

Tropocollagen, composed of three intertwining peptide strands with characteristic sequence Gly-X-Y, where X and Y are frequently Pro or Hyp, respectively, is the principal load-bearing protein in mammals. Sequence variations and post-translational processes, such as hydroxylation of proline to hydroxyproline, or large-scale mineralization of tropocollagen fibrils into osseous structures, are known to have a profound effect on its mechanical (e.g. tensile modulus) and physical (e.g. melting point) properties and to play key roles in certain human diseases. Furthermore, due to its ubiquity in mammalian tissue, ancient collagen is of interest to archaeologists, who have found that certain degradation processes show consistent reaction rate over archaeological timescales and therefore serve as molecular clocks. In this work we explore the role of confinement on the structure and stability of collagen-mimetic systems using molecular simulations. We use a fluctuation method to compute the tensile stress-strain relationship of a (Gly-Pro-Pro)7 oligopeptide in a variety of solvent systems. Second, we calculate the partial molar volume of collagen strands in these solvents, and compare the excess volume relative to the tropocollagen triple helix to quantify the effect of solvent pressure. Finally, we study the effect of confinement by mineral phase on the structure of collagen by comparison of SAXS/WAXS data against structural changes of a compressed collagen microfibril.

Adhesion to carbohydrates presented on epithelial cell surfaces is often the first step in bacterial infection.[1] The low efficacy of monovalent inhibitors is circumvented, like in nature, by the presentation of multiple copies of the carbohydrate ligand. A great deal of attention therefore has been directed towards the synthesis of glycopolymers.[1-3] Despite this large interest, the mechanism of the ‘cluster glycoside effect&’ is not fully understood.[2]
Although multivalent presentation of carbohydrates on a polymeric scaffold can lead to inhibitors with good affinity for the target lectin or bacterial toxin, these do not discriminate between proteins that preferentially bind the same epitope. From looking at structural biology information regarding the binding pocket of different lectins and toxins, glycopolymers can be better tailored to their target and gain some specificity.[1]
Here we present a tandem post-polymerization modification strategy to systematically probe the multivalent inhibition of two distinct lectins as a function of linker length, carbohydrate density, and glycopolymer chain length.[1] This tandem post-polymerization method has been optimized to gain the optimum length spacer between the polymer backbone and the pendant saccharide.[2]

[1] Richards, S-J.; Jones, M. W.; Hunaban, M. I.; Haddleton, D. M.; Gibson, M. I., Angew. Chem. Int. Ed. 2012, 51, 7812-7816.
[2] Jones, M. W.; Richards, S-J.; Haddleton, D. M.; Gibson, M. I. Polym. Chem.
2013, 4, 717 - 723.
[3] Gou, Y.; Richards, S-J.; Haddleton, D. M.; Gibson, M. I., Polym. Chem. 2012, 3, 1634.

Cellulose nanocrystals (CNCs) are a form of pure cellulose that is exceptionally strong and stiff, yet sustainable, biodegradable and biocompatible. Hence, understanding the physical behavior of natural products, such as aerogels made of CNCs, is of utmost importance in order to make them potential candidates to replace the petroleum-based products in the 21st century. To approach a basic understanding of the properties of these aerogels, our strategy is to quantify their mechanical properties using nanoindentation, and correlate that behavior with the statistical spatial distribution of cellulose-cellulose contact points by TEM tomography. The ultimate goal is to achieve a better understanding of the cellulose-cellulose bond properties under different environmental conditions. In this initial work CNCs were prepared from pure cotton cellulose by hydrochloric acid hydrolysis. The aqueous CNC dispersion was then subjected to oxidation, converting the surface primary hydroxyls to carboxylic acids, prior to forming the dry CNC aerogels. The mechanical properties of these highly porous CNC aerogels were characterized by nanoindentation using a flat cylindrical punch of about 100 µm diameter. The flat punch was indented 5 µm into the surface to ensure a constant contact area during the measurements. The dynamic storage modulus and loss factor (tan δ) were measured over a frequency range of 1 - 150 Hz. While the storage modulus increased slightly, the loss factor showed significant change over the frequency range. There are two main deformation mechanisms that contribute to the measured mechanical properties of the aerogels - buckling of CNCs aligned parallel to the loading axis, and elastic bending of CNCs oriented at an angle to the loading axis. We postulate that buckling of CNCs is the predominant damping mechanism in these aerogels. Although at lower frequencies the buckling mechanism dominates, the aerogel behaves as a stiffer material at frequencies higher than about 90 Hz. From our results, it is reasonable to infer that the elastic bending of the CNCs plays an enhanced role during deformation at higher frequencies - resulting in an increase in storage modulus and drop in the loss factor.

Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to organisms. Normal type I collagen is a heterotrimer and consists of two alpha-1 chains and one alpha-2 chain. A variation of the natural type I collagen molecule is the type I homotrimer, which consists of three alpha-1 chains, and has been found in fetal tissues, fibrotic tissues, carcinomas, and fetal and cancer cells in human. A mouse model of the genetic brittle bone disease, osteogenesis imperfect (oim), is characterized by a replacement of the alpha-2 chain by an alpha-1 chain, resulting in a homotrimer collagen molecule. Experimental studies of oim mice tendon and bone have shown reduced mechanical strength compared to normal mice. Atomistic studies have revealed that the homotrimers form local kinks at molecular level. How the local kinks affect the packing of collagen molecules at the microfibril level and the relationship between the molecular content and the decrease in strength is, however, still not clear.
Here we use molecular simulations to study the mechanical differences between the heterotrimer and homotrimer collagen microfibrils. The collagen microfibril models are generated based on the in situ structure of full length collagen type I molecule with the actual amino acid sequence of real mouse collagen sequence (Collagen, type I, alpha 1 and alpha 2 chain precursor [Mus musculus]). In silico mechanical tests and structural analyses of collagen microfibril models are performed to understand the effects of the replacement of alpha-2 chain of type I collagen at the microfibril level and to address the origin of brittle bone disease.
Our results suggest that the oim microfibril is less dense compared to the normal microfibril as a result of local kink formations at molecular level. Both normal and oim microfibril models have nonlinear stress-strain relations, which are consistent with previous experiments. We find that the homotrimer microfibril has an increased lateral spacing between collagen molecules in both dehydrated and hydrated conditions, which is coincided with experiments and suggests that the increased lateral spacing is not solely due to the higher hydrophobicity of the alpha-2 chain. Mechanical tests show a higher modulus of the normal (heterotrimer) compared to the oim (homotrimer) microfibril, which suggests a molecular mechanism that the increase of lateral distance in oim fibril, due to local kink formations, causes a decrease of the modulus. Furthermore, the water distributions in both models are analyzed to reveal the structural differences at molecular level. Our studies provide fundamental insight of the effect of the loss of alpha-2 chain at the molecular level and help understanding the molecular origin of the bone brittle disease at much larger length-scales.

Nvjp-1 protein is key component of Nereis jaw which is composed of roughly 90% protein, halogens (sim;8%) and Zn ions (sim;2%). However, the hardness and stiffness of the jaws are comparable to the human dentin (~1-2 GPa of hardness and 10-20 GPa of stiffness). Nvjp-1 protein contains over 25 mol% histidine amino acid and people believe the formation of metal-coodinate crosslink between histidine-rich Nvjp-1 protein and Zn ions dominates the structural stability and marvelous mechanical properties of Nereis jaw. The metal-coordinate bond is a flexible connection due to its variable bond strength in different chemical microenvironments. The strength of metal-coordinate bond decreases in the low pH condition and the bond strength is larger as pH value is higher. Moreover, unlike most covalent bonds whose rupture is usually irreversible, metal-coordinate bonds are able to reform after rupture.
Here we report a study on building a bottom-up molecular based model of Nvjp-1 protein. A detailed analysis of geometric and mechanical properties of the Nvjp-1 at different pH values by fully atomistic simulation using pH-MD is presented. We analyze the effect of pH and ion on the structure and mechanical properties of Nvjp-1 protein and to investigate the role of metal-coordinate cross-links in Nvjp-1 proteins. Our results suggest that metal-coordinate cross-links play a significant role in achieving the characteristic mechanical properties of this protein material and compare our results with the experimental measurements. We discuss the opportunity of synthesizing peptide materials with mutable properties in the presence of metal-coordinate cross-links.

The construction or the synthesis of nanostructured materials are an expanding field of research with emphasis especially in the mechanisms involved in the formation of these structures as well as the control of shape and size. In this context, fung were used as biotemplating to obtain nanostructured systems of metal nanoparticles with potential applications in development of sensors and biosensors. This work showed the use of fungus micellar to obtain self-assembled systems of gold and silver nanoparticles on the surface of hyphae, forming stable micro tubules structures and understanding the multilayers formation mechanisms. The fungi hyphae Aspergillus aculeatus were grown in an Erlenmeyer flask containing solution of Czapeck medium. After two weeks, the medium was removed for addition of the metal colloidal dispersion. The colloidal nanoparticles were characterized by X-ray diffraction and UV-Vis spectroscopy and, the micro tubules, by scanning electron microscopy. The results showed a facile route for self-organization of colloidal metal nanoparticles on living filamentous fungi aiming to fabricate micro tubular structures with typical diameter of 2-3 mu;m and lengths exceeding a few millimeters with dimensional tube system which is mechanically stable even after drying removal of the medium liquid. Gold nanoparticles easily formed a uniform surface on the cell wall. We observed that the thickness of the micro tubule could be controlled by modifying the initial nanoparticle concentration. The strength of interaction between particles is strong enough to form a solid wall structure that allows sectioning. This allows the various layers of particles that form a wall with a thickness of 300 nm. The first layer of metal nanoparticles was formed because the hydrophobic effect and the formation of strong covalent bonds between the metal and the sulfur residues of proteins in the cell wall. However, interestingly, metal particles still forming subsequent layers because the fungus produced metabolites by consume citrate that stabilizes gold nanoparticles. The metabolites of fungi adhered nanoparticles and this results in destabilization of the double electrical layer of metal colloidal nanoparticles causing adsorption on any surface, as it was shown in an experiment in which silicon plates placed in fungus + colloid solution and its surface was coated with nanoparticle. However, the silicon in presence only of the colloid has not occurred the adsorption. In this sense, the preparation of stable nanostructures as micro tubules opens the way for different technological applications as well as in the development of sensors and biosensors.

Amyloids are an exciting class of protein fibrils that have garnered much interest due to their role in a variety of severe neurological diseases, most notably Alzheimer's disease. More recently, they have also been considered for use as functional biomaterials due to their excellent mechanical properties as well as their high propensity to self-assemble. In general, the great mechanical performance of amyloid fibrils is derived from their beta-sheet rich secondary structure, but it is still not clear how the specific arrangement and organization of the beta sheets affects the mechanical properties at both the individual fibril scale and in collections of fibrils. We use full atomistic molecular dynamics simulations to investigate the force-displacement behavior of a variety of amyloid and amyloid-like protein fibrils, all of which feature a cross-beta motif in their secondary structures. We examine fibrils with parallel and antiparallel stacked beta sheet structures, beta-helical protein fibrils, as well as structures which combine these different motifs. Our results provide key insights into the mechanisms which govern the deformation behavior and mechanical response of amyloid and amyloid-like protein fibrils and can help to guide the design of amyloid-based functional materials.

Tissue engineering is the holy grail of regenerative medicine with lofty goals of tissue and organ replacement. Specifically, many challenges exist for bone tissue engineering, a prominent one being materials design of scaffolds that have optimized mechanical and degradation properties. Natural bone is a nanocomposite of hydroxyapatite (HAP) and type I collagen. Due to its excellent bioactivity, synthetic HAP has been widely investigated for use as a bone substitute. Previous work in our group on development of the ‘Altered Phase Theory&’ of polymer clay nanocomposites has inspired the use of nanoclays in scaffold materials. Addition of montmorillonite clay to polymer scaffolds enhances the mechanical properties of the scaffolds and forms a polymer-clay nanocomposite. We have developed biomineralized HAP using amino acid modified nanoclays. Amino-acid-modified montmorillonite clay with biomineralized hydroxyapatite (in-situ HAP clay) has been shown by our group to enhance osteoconductive properties of polymer scaffolds. In this work we report Electron Energy Loss Spectroscopy (EELS) studies on the biomineralized nanoclay to determine the extent of interaction of HAP with the modified clay in in-situ HAP. The core loss K-edge of oxygen (532 eV) and the L2,3-edge for calcium (346 eV) in the HAP, modified clay and in-situ HAP clay systems were investigated and the energy-loss near-edge structures (ELNES) were compared. Differences in the calcium L2,3-edge and oxygen k-edge values for in-situ HAP clay vs. HAP and modified clay were observed. These differences are compared with the atomic interaction energy calculations conducted our group for the in-situ HAP clay system using molecular dynamics simulations. In addition, we have conducted similar studies on diseased bone (with Osteogenesis imperfecta). Electron energy loss spectroscopy is used to determine the oxygen K-edge, calcium L2,3- edge and ELNES for normal human bone and osteogenesis imperfecta bone. These experimental studies describe new insights into the molecular basis of bone diseases.

Many biomechanical imaging techniques have been developed for soft tissue characterization and tumor detection based on the differentiation of the mechanical properties in normal and pathologic tissues. Among them, acoustic radiation force imaging is an apposite imaging method using focused ultrasound to internally excite the tissue. The elastograms are obtained by measuring the responses of the excited tissue with ultrasound. Generally, the heterogeneity of soft tissue is simplified by a piecewise homogeneous model with kernel size on the order of 1mm. However, realistic breast tumors still have strong heterogeneity below the millimeter scale, and the piecewise homogeneous model cannot capture the true behavior of the underlying tissue. In order to verify the piecewise homogeneity simplification, a finite element model is built to describe the breast tumor heterogeneity in acoustic radiation force imaging. In the simulation, domains of the tumors (1 and 3mm spheres) are considered homogeneous for the piecewise homogeneous case. Within each domain, the average elasticity of the tumor is kept the same, while we study two scenarios: a) gradual changes of the tumor elasticity using a Gaussian function, and b) discrete subzones with randomly assigned tumor elasticity. For the first case, compared to the case of piecewise homogeneity, the responses inside the tumors are additionally affected by a new parameter, the standard deviation of the Gaussian function, which describes the heterogeneity below the millimeter scale. For the second case, the tumors are divided into approximately equal sized subzones with randomly assigned elasticity. For relatively large subzones, the results suggest that averaging the displacement over a larger region in the focal zone leads to more consistent results with that of the piecewise homogeneous model at the expense of reduced spatial resolution. As the size of the subzones decreases, the responses converge to the piecewise homogeneous case.

Self-healing properties have been traditionally added to resins. Typically the procedure implied the mixing of the fluid resin, resin catalyst and/or accelerator, microcapsules filled with monomer and first generation Grubbs catalyst. As the polymerization of the resin is completed a solid material that embeds within the polymeric matrix microcapsules filled with monomer (usually dicyclopentadiene) and first generation Grubbs catalysts is obtained. These "ingredients" are adding self-healing capabilities to the polymeric matrix (hardened resin). These self-healing capabilities are triggered by propagating cracks produced by the stress acting of the polymer. The cracks are generating a differential shear stress on the surface of the microcapsule that finally will rupture the microcapsule releasing the monomer, which starts its diffusion within the polymeric matrix and eventually reaches a first generation Grubbs catalyst. The interaction between the first generation Grubbs catalyst and the monomer (dicyclopentadiene) results in the polymerization of a new polymer (polydicyclopentadiene) within the polymeric matrix via a ring opening mechanism. Later, the process has been extended to polymers, by using the solution path (i.e. dissolving the polymer in an appropriate solvent and mixing it gently with microcapsules filled with monomer and first generation Grubbs catalyst. The process requires to find a solvent that does not dissolve the microcapsule and does not deactivate the catalyst.
We report on the addition of self-healing capabilities to a water soluble polymer (polyvinyl alcohol). To achieve this, the polymer has been dissolved in water. The first generation Grubbs catalyst has been added to the 10 % polymer solution. The mixture has been sonicated for 10 minutes by using a high power sonication. After that microcapsules filled with monomer (dicyclopentadiene) have been added to the mixture and gently homogenized by stirrinh. The solvent (water) was allowed to slowly evaporate for about 1 day in a vacuum oven at about 75 , and dog bone specimen were obtained from the as deposited films.
The presence of the monomer within the microcapsule has been confirmed by both Raman and FTIR measurements. The ring-opening polymerization has been supported by Raman spectroscopy. Finally, the self-healing capability has been supported by mechanical tests
(load-displacement measurements) at a very low displacement rate (0.01 mm/s) by using a TestResources equipment.

Natural active structures, such as cellular cytoskeletons, utilize dynamic networks of mechanochemical molecules and protein filaments for adaptive behavior modulation. Such components can be synthetically altered at a single molecule, and systems level to form new engineered materials. In particular, much potential exists in modifying myosin motor proteins, alpha-actinin binding proteins, and actin filaments to develop smart contractile materials that retain robust performance for varied design requirements and across environmental fluctuations.
Here, we developed an agent-based simulation platform to explain (and predict in novel variations) the emergent performance of complex mechanochemical molecular interactions. The platform consists of a virtual environment in which autonomous software agents represent synthetic molecules that interact with an actin filament traveling at a steady state. Agents were configured with varied macromolecular geometries, attachment rates, and detachment rates that influenced how agents stochastically behaved during each simulation step. System performance was measured with respect to ATPase rate, force, velocity, and stability. The emergent agents&’ behaviors were found to reliably reproduce quantitative relationships describing the hyperbolic force-velocity curve of myosins, sigmoid force-velocity curve of myosin and alpha-actinin, and the linear dependence of velocity on myosin detachment rate and step size.
We then investigated system performance with respect to varied design objectives, such as high energy efficiency, power density, and stability. Optimal systems were identified via engineering optimization methods. When trade-offs among multiple design objectives were considered, we found that rather than configuring new systems for each objective, it was possible to design a single robust system that performed well for all conditions by modulating its behavior through biochemical signaling to adapt to its environment. The discovery of such systems has potential for enabling higher performance and economical active material systems, where many potential applications exist in biomedicine and nanotechnology endeavors.

The field of computational cell mechanics encompasses different scales ranging from individual monomers, cytoskeleton constituents, full cell, up to small networks. Its focus, fueled by the development of interdisciplinary collaborative efforts between engineering, computer science, biology and medicine, until recently relatively isolated, has allowed for important breakthroughs in biomedicine, bioengineering or even neurology. Among all cells, neurons are at the heart of tremendous medical challenges (traumatic brain injuries, Alzheimer's disease, etc.). In nearly all of these challenges, the intrinsic coupling between mechanical, biochemical and electrophysiological mechanisms is of drastic relevance. This presentation aims at highlighting the role of such coupling through a set of relevant modeling efforts aimed at relating mechanical damage and cell functional alteration.

Fluids filling porosity at small length scales play an important role in the creep behavior of microheterogeneous materials. In more detail, nanoconfined fluid-filled interfaces are typically envisioned to act as a lubricant, once electrically charged solid surfaces start to glide along fluid sheets . Thereby, the fluid is typically in a liquid crystal state, referring to an “adsorbed”, “ice-like”, or “glassy” structure of fluid molecules , . Here, we aim at translating liquid crystal physics and the related viscous interface behavior into apparent creep laws at the continuum scale of materials consisting of one non-creeping solid matrix hosting almost flat fluid-filled interfaces . The liquid crystal behavior, is modeled, at the interface scale, by a linear relationship between the rate of relative displacements of neighboring fluid layers, on the one hand, and corresponding interface eigentractions, on the other hand, with an interface viscosity as the proportionality constant. Homogenization schemes for eigenstressed heterogeneous materials are used to upscale this interface behavior to the significantly larger observation scale of a matrix-inclusion composite comprising a homogeneous, isotropic, and linear elastic solid matrix, and embedded interacting, circular, and parallel interfaces. Our model describes, in an analytical fashion, how the macroscopic loading, the elastic properties of the solid, as well as the size, the density, and the viscosity of the interfaces influence the creep behavior of the composite under prescribed macroscopic stresses. The multiscale model suggests that the speed of the interfacial displacement evolution decreases exponentially with increasing time, such that viscosity-related interface eigentractions decrease exponentially down to zero. The envisioned liquid crystal-based interface behavior manifests itself at the significantly larger scale of the composite as creep of macrostrains, exhibiting again exponentially decaying deformation rates, as reported e.g. for biological tissues such as bones .

The human bone is a complex hierarchically organized nanocomposite structure made up mostly of collagen and hydroxyapatite. Genetic alterations are known to trigger specific structural nuances to the triple helical collagen structure and are often manifested as various health conditions of bone. We have also conducted experimental studies on nanomechanical testing of human cadaver bone samples. Here, we report a comprehensive study of development of multiscale models of fibrillar structures in human bone that incorporate orientational and structural details of collagen-hydroxyapatite interactions in bone. We have also described the mechanics of the full length (300 nm) collagen molecule that is structurally accurate to the collagen length in human bone. Simulations on the full length collagen reveal a third tier hierarchy in the structure of collagen that was not observed before. Collagen structure is made up of a helical arrangement (tier two) of three peptide chains that are each helical (tier one). We have discovered a third helicity in the helical arrangement of the triple helical molecule (tier three). Mechanical behavior of the three tiers indicated the resplendent nature of strengthening mechanisms that are worthy of biomimetic design, resulting from years of evolution. Molecular models of mineral-protein structures in bone have been developed. Steered molecular dynamics (SMD) is used to describe the molecular behavior and mechanics of collagen molecule in the proximity of hydroxyapatite in various different orientations. We observe that the mechanical response of collagen is significantly altered by the proximity and orientation of hydroxyapatite. A finite element (FEM) model of a collagen fibril of 50 nm diameter, and a micron length is built that is representative of the staggered arrangement of collagen molecule in human bone. The results from steered molecular dynamics are incorporated into the FEM model. The deformation characteristics and parameters of collagen and the collagen-hydroxyapatite molecular interfaces used in FEM model are directly obtained from steered molecular dynamics. We also present results of our simulation carried out in the large-displacement regime.

A combination of increased fall rates and reduced bone strength in osteoporotic patients rises the risk of hip fractures in the elderly. Osteoporotic fractures are associated with a cost of ~$20 billion per year in the United States and ~$30 billion per year in the European Union. Knowledge of bone mechanical properties and fracture strength is now required to help understand this epidemic. Computed tomography-based finite element analysis (QCT/FEA) has emerged as a very promising method used to asses bone stiffness and strength. However, QCT/FEA clinical implementation requires a unified modeling procedure, consistency in predicting bone mechanical properties, and validation with realistic test data that represent typical hip fractures.
One hundred cadaveric femora with bone densities varying from normal to osteoporotic were first CT-scanned and then fracture-tested to build, refine, and validate QCT/FEA models of femoral fractures. Image reconstructions of fractured femora were created from post-fracture CT scans to classify fracture types. Load cells were used to measure forces leading to fracture and the fracture events were recorded from both sides using high-speed video cameras.
An analysis of experimental data revealed that the final failure of the femoral cortex occurred after the peak force for 96% of the femora. Fracture forces were smaller in osteoporotic femora compared to osteopenic and normal femora and correlated moderately with bone density but weakly with age and femoral geometry. Fracture types and fracture loads were also weakly correlated. Regions of large von Mises strains obtained from digital analysis of high-speed video images correlated very well with locations of damage initiation and fracture pattern for 94% of the femora. An in-situ method developed to determine the density-elastic modulus relationship improved significantly the QCT/FEA prediction of femoral stiffness.
This study provides evidence that QCT/FEA methods hold promise for use in clinical settings. With additional improvements a robust model can be developed with high levels of confidence in its ability to predict patient specific hip fracture from CT scans.

We studied the structure and mechanical properties of DNA i-motif nanowires by means of molecular dynamics computer simulations. We built up to 230 nm-long nanowires, based on a repeated TC5 sequence from crystallographic data, fully relaxed and equilibrated in water. The unusual C#9679;C+ stacked structure, formed by four ssDNA strands arranged in an intercalated tetramer, is here fully characterized both statically and dynamically. By applying stretching, compression and bending deformations with the steered molecular dynamics and umbrella sampling methods, we extract the apparent Young&’s and bending moduli of the nanowire, as well as estimates for the tensile strength and persistence length. According to our results, i-motif nanowires share similarities with structural proteins, as far as their tensile stiffness, but are closer to nucleic acids and flexible proteins, as far as their bending rigidity is concerned. Curiously enough, their tensile strength makes such DNA fragments tough as a mild steel or a nickel alloy. Besides their yet to be clarified biological significance, i-motif nanowires may qualify as interesting candidates for nanotechnology templates, due to such outstanding mechanical properties.

Our objective is to develop a model for nanostructured biomaterials that form through the self-assembly of different amphiphilic lipid species. Individual lipid molecules are represented by a hydrophilic head group and two hydrophobic tails. The lipid species can differ in terms of specific chemical properties of the polar head groups and the hydrocarbon tail groups. The lipid molecules form a stable hybrid vesicle via the self-assembly in the presence of a hydrophilic solvent due to their amphiphilic nature. We investigate the factors that control the self-organization of the nanoscopic components of the hybrid soft biomaterials. We use a Molecular Dynamics-based mesoscopic simulation technique called Dissipative Particle Dynamics which simultaneously resolves the structure and dynamics of the nanoscopic building blocks and the hybrid aggregate. In this presentation, we characterize the morphology and dynamics of the various hybrid nanostructures. The morphological analysis of the hybrid aggregates and their material characterization can be combined to predict the structural and dynamical properties of other hybrid biomaterials.

Hydroxyapatite (HAP) (chemical formula: Ca10(PO4)6(OH)2) is the basic mineral component of mammalian bone and tooth enamel. The mechanical behavior of the bone depends on complex interplay between the hard inorganic apatite phase and the soft collagen matrix. Components in human bones are usually non-stoichiometric where Ca/P molar ratio varies from 1.5 to 1.67 for calcium deficient case, whereas the same is 1.67 for stoichiometric case. Osteoporosis is the most important underlying cause of fractures in the elderly and is a progressive metabolic disease that involves a decrease in the bone mass density with a concomitant decrease in the Ca/P ratio. For the development of effective therapeutic treatments for osteoporosis, it is imperative to understand the exact nature of the changes in mechanical behavior as a function of bone chemistry. While it is recognized that a nominal calcium deficiency in the inorganic phase leads to brittle bones, the local variation in structural and mechanical response of the inorganic constituent with varying calcium content is poorly understood.
Experimental results in the literatures show that, when Ca/P ratio changes from 1.67 to about 1.5, there will be an 80% drop in the elastic modulus and hardness and 75% reduction in toughness, which is correlated with the presence of associated defects. In this study, we have analyzed the theoretical aspects of the effect of calcium deficiency on structural and mechanical behavior of HAP using first-principles calculations, which is an ideal approach to study the precise role played by the point defects. Our calculations are based on density functional theory (DFT) as implemented in the Quantum Espresso package with a generalized gradient approximation (GGA) to exchange correlation energy of electrons, and ultrasoft pseudopotentials to represent interaction between ionic cores and valence electrons.
The calculated values of lattice constants and bulk modulus for the stoichiometric HAP are in good agreement with experimental and theoretical results reported earlier. The vacancy formation energy and five independent elastic constants are calculated for different vacancy structures of Ca-deficient HAP (Ca-dHAP). We report the existence of a metastable state, for one of the Ca-HAP defect structure, under applied pressure, which could be the reason for experimentally reported drastic reduction in the modulus and hardness for the non-stoichiometric case. The structures of stoichiometric and nonstoichiometric HAP&’s are analyzed and compared in detail using bonding characteristics and charge density plots and are correlated to their observed elastic behavior. DFT linear response is used to determine dynamical matrices on a mesh of wave vectors, which are Fourier interpolated to obtain full phonon dispersion for stoichiometric HAP and for different vacancy structures. IR active modes are analyzed, which could be useful in experimental characterization of the Ca-dHAP.

Bisphosphonates are the primary pharmacologic treatment for osteoporosis and typically reduce fracture risk by 30-50% in postmenopausal women. Atypical femoral fractures, characterized by a transverse morphology indicative of a brittle fracture, have recently emerged as a rare but serious side effect of bisphosphonate treatment. Because bisphosphonates reduce bone remodeling, they have the potential to alter bone tissue material properties. Thus, the objectives of this study were (1) to compare the nanomechanical properties of bone tissue from patients with atypical femoral fractures to that of patients with typical osteoporotic fragility fractures, and (2) to correlate the nanomechanical properties with compositional properties. Specimens of proximal femoral cortical bone were obtained from postmenopausal osteoporotic women with atypical fractures (n=2) and compared to control patients with typical osteoporotic fractures (n=2). All specimens were sectioned and polished, and nanomechanical properties were assessed with nanoindentation. The mechanical properties were then compared to compositional properties as assessed with FTIR imaging. When nanomechanical properties were examined within each specimen, less variability in reduced modulus and hardness was observed in atypical fracture specimens (mean COV= .142) than in control specimens (mean COV= .160). When all specimens were pooled, collagen maturity was the strongest predictor of reduced modulus, but did not correlate strongly with hardness. These results are consistent with prior studies showing reduced cortical bone heterogeneity with bisphosphonate treatment in postmenopausal women with fragility fractures.

Microalgae are extremely abundant and important microorganisms, which affect a variety of environmental factors. Microalgae create almost half of the oxygen in the atmosphere and als