Structure-function Relationships Research Articles

Insight into the Coordination Environment of Ru Single-Atom for Dry Reforming of Methane.

Dry reforming of methane (DRM), a pivotal process for converting greenhouse gases into syngas is demanding rationally designed catalysts with high stability and ideal catalytic performance for industrial applications due to its stability of reactant molecules and characteristic of carbon deposition. However, the mechanistic understanding of how the coordination environment of the metal in a single-atom catalytic system may influence the catalytic performance remains limited. In this work, high- and low-coordinating Ru-based (RuHC and RuLC) catalysts with distinct Ru-O coordination numbers are prepared using one-pot and two-step methods. The difference in the stability (12.3% and negligible deactivation during 20 h test for RuLC and RuHC catalysts respectively) and selectivity (0.57 and 0.37 of H2/CO ratio) brought by the coordination environment signified the structure-function relationship of single-atom catalysts in DRM. The impact of the structure on the properties is systematically investigated by thorough structural and operando characterization as well as density functional theory (DFT) calculation. The findings contribute to the optimal design of single-atom catalysts for DRM, offering a theoretical basis for industrial catalyst development and the potential to improve the process's environmental impact.

Zwitterionic Peptides: From Mechanism, Design Strategies to Applications.

Zwitterionic peptides, as a type of peptide composed of charged residues, are electrically neutral, which combine the advantages of zwitterionic materials and biological peptides, exhibiting hydrophilicity and programmable properties. As attractive candidates for resisting nonspecific adsorption of biomacromolecules and microorganisms, zwitterionic peptides have been applied in materials science, biomedicine, and biochemistry over the past decade. In this review, the development of zwitterionic peptides has been systematically outlined and analyzed, including their mechanisms, structure-function relationships, and design strategies. Furthermore, this review emphasizes and discusses their recent applications for developing functional coatings, biosensors, drug delivery systems, and engineering proteins. Finally, future research perspectives and challenges of zwitterionic peptides are also prospected and discussed. This review is intended to provide clarity and insight into the design and applications of zwitterionic peptides.

Structural characterization, antioxidant activities and physicochemical properties analysis of a galactose-rich exopolysaccharide produced by Limosilactobacillus fermentum YL-11

Lactobacilli-derived exopolysaccharides (EPSs) are widely regarded as safe and have been employed as potential natural, non-toxic additives and functional agents in food industry. The structural properties of a galactose-rich exopolysaccharide produced by Limosilactobacillus fermentum YL-11 (YL-11 EPS) were investigated with chemical and instrumental analysis. The YL-11 EPS was determined to have a molecular weight (Mw) of 13.2 kDa. Nine different types of glycosidic bonds were identified in YL-11 EPS. The inferred structure of the YL-11 EPS contained the backbone of →2)-β-D-Galp-(1→[3)-β-D-Galp-(1]4 → 3)-β-D-Galp-(1 → 3)-β-D-Galp-(1→, with two side chains, β-D-Galp-(1 → 6)-α-D-Manp-(1 → 6)-[α-D-Glcp-1→2]-α-D-Manp-(1 → 3)-[α-D-Glcp-1→6]-α-D-Glcp-(1 → 3)-[α-D-Glcp-1→6]-α-D-Glcp-(1→ with an acetyl group at the O-3 position of →2,6-α-D-Manp-1→ and α-L-Araf-(1→, which were present at the C6 location of the 1,3-β-D-Galp. The YL-11 EPS showed concentration-dependent antioxidant activities and the DPPH, ABTS, hydroxyl groups and superoxide radicals scavenging rates of 10 mg/mL YL-11 EPS reached 61%, 74%, 35.4% and 40%, respectively. The YL-11 EPS also has a beneficial protective impact on H2O2-injured cells, which pretreatment with YL-11 EPS can substantially decrease ROS levels and enhance SOD enzyme activity. Additionally, the YL-11 EPS exhibited good thickening properties and thermal stability. The EPS's structural information and physicochemical properties provide a basis for studying their structure-function relationships.

Synergistic Coordination Effect and Metal-Support Interaction Engineering of Single-Atom Mn-N2 Sites for Boosting Sensitive and Selective Dopamine Biosensing in Human Serum.

Coordination environment of metal atoms is core for designing high-performance single-atom catalysts (SACs), while metal-support interaction also has an important effect on structure-function relationship. Nevertheless, the interaction effect of metal-support is mostly ignored. Through synergistic regulation of coordination environment and metal-support interaction, Mn SAC with atom-dispersed Mn-N2 sites on dopamine (DA) support is synthesized for sensitive and selective DA oxidation based on theoretical calculations and experimental explorations. MnN2 presents the more optimal catalytic site for DA oxidation than other coordination conditions, enhancing sensitivity including a wide range, a low limit of detection, and particularly a very low catalytic potential. The construction of Mn-N2 active sites on DA carbon promotes the coupling between Mn metal atoms and DA support, decreasing work function, facilitating electron exchange, shortening response time, and boosting selectivity. Both the catalytic mechanism of Mn SAC toward DA and the relation construction of catalyst's structure and catalytic function are established.

Multimodal evidence for cerebellar influence on cortical development in autism: structural growth amidst functional disruption.

Despite perinatal damage to the cerebellum being one of the highest risk factors for later being diagnosed with autism spectrum disorder (ASD), it is not yet clear how the cerebellum might influence the development of cerebral cortex and whether this co-developmental process is distinct between neurotypical and ASD children. Leveraging a large structural brain MRI dataset of neurotypical children and those diagnosed with ASD, we examined whether structural variation in cerebellar tissue across individuals was correlated with neocortical variation during development, including the thalamus as a coupling factor. We found that the thalamus plays a distinct role in moderating cerebro-cerebellar structural coordination in ASD. Notably, structural coupling between cerebellum, thalamus, and neocortex was strongest in younger childhood and waned by early adolescence, mirroring a previously undescribed trajectory of behavioral development between ASD and neurotypical children. Complementary functional connectivity analyses likewise revealed atypical connectivity between cerebellum and neocortex in ASD. This relationship was particularly prominent in a model of cerebellar structure predicting functional connectivity, where ASD and neurotypical children showed divergent patterns. Interestingly, these functional-structural relationships became more prominent with age, while structural effects were most prominent earlier in childhood, and showed significant lateralization. This pattern may suggest a developmental sequence where early uncoordinated structural growth amongst regions is followed by increasingly atypical functional synchronization. These findings provide multimodal evidence in the living brain for a cerebellar diaschisis model of autism, where both increased cerebellar-cerebral structural coupling and altered functional connectivity in cerebro-cerebellar pathways contribute to the ontogeny of this neurodevelopmental disorder.

Bayesian inference of frequency-specific functional connectivity in MEG imaging using a spectral graph model

Abstract Understanding the relationship between structural connectivity (SC) and functional connectivity (FC) of the human brain is an important goal of neuroscience. Highly detailed mathematical models of neural masses exist that can simulate the interactions between functional activity and structural wiring. These models are often complex and require intensive computation. Most importantly, they do not provide a direct or intuitive interpretation of this structure–function relationship. In this study, we employ the emerging concepts of spectral graph theory to obtain this mapping in terms of graph harmonics, which are eigenvectors of the structural graph’s Laplacian matrix. In order to imbue these harmonics with biophysical underpinnings, we leverage recent advances in parsimonious spectral graph modeling (SGM) of brain activity. Here, we show that such a model can indeed be cast in terms of graph harmonics, and can provide a closed-form prediction of FC in an arbitrary frequency band. The model requires only three global, spatially invariant parameters, yet is capable of generating rich FC patterns in different frequency bands. Only a few harmonics are sufficient to reproduce realistic FC patterns. We applied the method to predict FC obtained from pairwise magnitude coherence of source-reconstructed resting-state magnetoencephalography (MEG) recordings of 36 healthy subjects. To enable efficient model inference, we adopted a deep neural network-based Bayesian procedure called simulation-based inference. Using this tool, we were able to speedily infer not only the single most likely model parameters, but also their full posterior distributions. We also implemented several other benchmark methods relating SC to FC, including graph diffusion and coupled neural mass models. The present method was shown to give the best performance overall. Notably, we discovered that a single biophysical parameterization is capable of fitting FCs from all relevant frequency bands simultaneously, an aspect that did not receive adequate attention in prior computational studies.

Strain-dependent glutathionylation of fibronectin fibers impacts mechano-chemical behavior and primes an integrin switch

The extracellular matrix (ECM) is a protein polymer network that physically supports cells within a tissue. It acts as an important physical and biochemical stimulus directing cell behaviors. For fibronectin (Fn), a predominant component of the ECM, these physical and biochemical activities are inextricably linked as physical forces trigger conformational changes that impact its biochemical activity. Here, we analyze whether oxidative post-translational modifications, specifically glutathionylation, alter Fn’s mechano-chemical characteristics through stretch-dependent protein modification. ECM post-translational modifications represent a potential for time- or stimulus-dependent changes in ECM structure-function relationships that could persist over time with potentially significant impacts on cell and tissue behaviors. In this study, we show evidence that glutathionylation of Fn ECM fibers is stretch-dependent and alters Fn fiber mechanical properties with implications on the selectivity of engaging integrin receptors. These data demonstrate the existence of multimodal post-translational modification mechanisms within the ECM with high relevance to the microenvironmental regulation of downstream cell behaviors.

Upcycling of polyethylene waste to biodegradable adhesive and coating via Baeyer-Villiger reaction: A new view on oxidation-fracture mechanism and structure-function relationship

Non-biodegradable polyethylene waste accumulates in large quantities in the environment posing a serious threat to the survival of creatures. Meanwhile, polyethylene suffers from inherent polarity limitations that curtails its application scope. Oxidation is an efficient approach of upcycling waste polyethylene through introduction of hydrophilic functional groups (such as –COOH, –OH), yet often at the expense of their original hydrophobicity. Herein, the hydrophobic ester groups, were introduced via Baeyer-Villiger oxidation to ingeniously balance the contradiction among hydrophobicity, interfacial forces and sustainability of polyethylene oxidation products. A tandem conversion mechanism among the oxidative groups was proposed while the decrease in molecular weight and branching degree was clarified to be a result of β-scissions occurring the branches during the oxidation. Meanwhile, the effect of oxidation degree and molecular weight on interfacial forces was revealed. The excellent hydrophobicity and corrosion resistance of the oxidized polyethylene coating can be attributed to the low content of carboxyl/hydroxyl groups, rich hydrophobic ester groups and the retained long carbon chain structure. Besides, the introduced ester groups and lower molecular weight also provided the oxidation products with potential biodegradability. This work provided a new insight on the Baeyer-Villiger oxidation of polyethylene and the potential for upcycling of polyethylene waste into sustainable materials.

Exploration and Design of Carbon Dot-Based Long Afterglow Materials Using Active Machine Learning and Quantum Chemical Simulations.

Long afterglow materials based on carbon dots (CDs) have attracted extensive attention in the field of optics due to their low cost and nontoxic properties. However, the targeted synthesis of specific properties of complex and unknown structures such as CDs remains a daunting challenge. In this study, the powerful nonlinear fitting ability of machine learning was used to explore the afterglow properties of CDs. The XGBoost algorithm demonstrates high prediction accuracy in determining the optimal excitation wavelength, optimal emission wavelength, and afterglow lifetime. Using Bayesian optimization, we screened and synthesized the CDs-based long afterglow materials with the longest lifetime reported so far by a one-step microwave method. By combining quantum chemical calculations with experimental data, we revealed the structure-function relationship between CDs and their precursors through electron-hole analysis. These results show that machine learning can establish nonlinear correlations between precursors and materials with unknown structures, clarify their intrinsic relationships, simplify the material design process, and thus accelerate the development of advanced materials.

Establishing a Robust Nonlinear Targeted Switch for C1 Electroproduction in Atomic Alloy Cox/Pd Bimetallenes.

Establishing a targeted switch for CO2 conversion under electric drive is essential for achieving carbon-balance by enabling selective chemicals. However, engineering the topological assembly of active sites to precisely regulate the competing pathways for various intermediates has been plagued by unclear structure-function relationships. To tailor the CO/formate pathways, herein we established a robust nonlinear targeted switch with tunable active Cox sites integrated into Pd metallene, which involves Co1/Pd single-atom alloy (favoring CO) and Co2/Pd diatomic alloy (favoring formate). Transitioning from Co1/Pd to Co2/Pd atomic alloy bimetallenes resulted in a nonlinear, high-contrast flip in selectivity, surpassing 94 % for CO and formate productions in both H-cell and flow cell. Furthermore, the superior selectivity and current efficiency for CO (>80 %) and formate (>88 %) were consistently maintained at -150 mA cm-2 over continuous 200 h. Theoretical simulations and in situ spectroscopy analyses unveiled that appropriate adjacent metal site combinations (Pd-Pd, Pd-Co and Co-Co) lead to tunable dz 2 band center and a nonlinear shift in preferred adsorption configurations of intermediates, dictating the C1 pathways. Our finding reveals a desired switch in C1 selectivity and robust stability within Cox/Pd system, providing a new perspective for fine-tuning energy conversion processes through specific topological assembly.

Conformational Selection of α-Synuclein Tetramers at Biological Interfaces.

Controlling the polymorphic assemblies of α-synuclein (αS) oligomers is crucial to reroute toxic protein aggregation implicated in Parkinson's disease (PD). One potential mediator is the interaction of αS tetramers with cell membranes, which may regulate the dynamic balance between aggregation-prone disordered monomers and aggregation-resistant helical tetramers. Here, we model diverse tetramer-cell interactions and compare the structure-function relations at the supramolecular-biological interface with available experimental data. The models predict preferential interaction of compact αS tetramers with highly charged membrane surfaces, which may further stabilize this aggregation-resistant conformer. On moderately charged membranes, extended structures are preferred. In addition to surface charge, curvature influences tetramer thermodynamic stability and aggregation, with potential for selective isolation of tetramers via regio-specific interactions with strongly negatively charged micelles that screen further aggregation. Our modeling data set highlights diverse beneficial nano-bio interactions to redirect biomolecule assembly, supporting new therapeutic approaches for PD based on lipid-mediated conformational selection and inhibition.

Structure–Function Relationships and Health-Promoting Properties of the Main Nutraceuticals of the Cactus Pear (Opuntia spp.) Cladodes: A Review

Over the past decade, several studies have established a direct link between functional foods, nutraceuticals, and a reduced risk of oxidative-stress-related diseases. Nutraceuticals, which encompass a variety of bioactive molecules, exhibit both nutritional and therapeutic properties. The cactus pear (Opuntia spp.) is a plant genus with many species recognized as functional foods, largely attributed to their high content of nutraceuticals, including polyphenols, fatty acids, vitamins, amino acids, pigments, and phytosterols. These compounds of different structures and functions possess different biological activities, contributing to the health-promoting properties of cactus pear. This makes cactus pears a valuable plant for the food, cosmetic, and pharmaceutical industries. While extensive research has focused on the nutritional profile of cactus pear fruits, the cladodes have received comparatively limited attention. Notably, the nutritional composition of cladodes can exhibit considerable variability, influenced by species and growing conditions. Furthermore, although various bioactive compounds have been identified in cladodes, studies elucidating their mechanisms of action, health benefits, and potential therapeutic applications remain insufficient. Addressing these gaps is crucial for enhancing the understanding and utilization of cactus pear cladodes. This paper provides a comprehensive overview of the structure–function relationships of the main nutraceuticals found in cactus pear cladodes. It synthesizes data from recent and relevant literature to elucidate the content of these compounds in relation to species and geographical origin, while also detailing the main biological activities and health-promoting benefits associated with cactus pear cladodes.

Comprehensive Insights into Microbial Lipases: Unveiling Structural Dynamics, Catalytic Mechanism, and Versatile Applications.

Microbial lipases (MLs) are pivotal biocatalysts in lipid biotechnology due to their diverse enzymatic properties and substrate specificity, garnering significant research attention. This comprehensive review explores the significance of MLs in biocatalysis, providing insights into their structure, catalytic domain, and oxyanion hole. The catalytic mechanism is elucidated, highlighting the molecular processes driving their efficiency. The review delves into ML sources, spanning fungi, yeasts, bacteria, and actinomycetes, followed by a discussion on classification and characterization. Emphasizing the scattered findings in the literature, the paper consolidates the latest information on ML applications across various industries, from food and pharmaceuticals to biofuel production and the paper and pulp industry. The review captures the dynamic landscape of ML research, emphasizing their structure-function relationships and practical implications across diverse sectors.

Electrophysical cardiac remodeling at the molecular level: Insights into ryanodine receptor activation and calcium-induced calcium release from a stochastic explicit-particle model

We present the first-ever, fully discrete, stochastic model of triggered cardiac Ca2+ dynamics. Using anatomically accurate subcellular cardiac myocyte geometries, we simulate the molecular players involved in Ca2+ handling using high-resolution stochastic and explicit-particle methods at the level of an individual cardiac dyadic junction. Integrating data from multiple experimental sources, the model not only replicates the findings of traditional in silico studies and complements in vitro experimental data but also reveals new insights into the molecular mechanisms driving cardiac dysfunction under stress and disease conditions. We improve upon older, nondiscrete models using the same realistic geometry by incorporating molecular mechanisms for spontaneous, as well as triggered calcium-induced calcium release (CICR). Action potentials are used to activate L-type calcium channels (LTCC), triggering CICR through ryanodine receptors (RyRs) on the surface of the sarcoplasmic reticulum. These improvements allow for the specific focus on the couplon: the structure-function relationship between LTCC and RyR. We investigate the electrophysical effects of normal and diseased action potentials on CICR and interrogate the effects of dyadic junction deformation through detubulation and orphaning of RyR. Our work demonstrates the importance of the electrophysical integrity of the calcium release unit on CICR fidelity, giving insights into the molecular basis of heart disease. Finally, we provide a unique, detailed, molecular view of the CICR process using advanced rendering techniques. This easy-to-use model comes complete with tutorials and the necessary software for use and analysis to maximize usability and reproducibility. Our work focuses on quantifying, qualifying, and visualizing the behavior of the molecular species that underlie the function and dysfunction of subcellular cardiomyocyte systems.

Visual Field Patterns in Optic Neuropathy

The optic nerve is susceptible to a wide variety of pathological processes. In optic neuropathy, quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guiding treatment plans. While acquired visual field defects may progress rapidly, congenital visual field defects may not progress or may progress slowly. Although the most common defect in congenital or acquired optic neuropathy is the central defect, many defect types that are not pathognomonic to the disease can be seen. In ischemic optic neuropathy, which is common among optic neuropathies, arcuate defect and central defect are usually seen. In disc disorders with localized nerve damage, such as optic disc coloboma or optic pit, localized defects such as arcuate scotoma or cecocentral scotoma in which the fixation point is preserved may be observed. Papilledema causes peripapillary fluid accumulation and an enlarged blind spot in the perimetry. In compressive optic neuropathies, non-specific defects such as central and subtudinal defects may be observed, as well as quadrant defects such as hemianopsia and quadrionopsia. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine structure-function relationships improves clinical care in neuro-ophthalmic disorders.

Tailoring the natural rare sugars D-tagatose and L-sorbose to produce novel functional carbohydrates

This multidisciplinary study details the biosynthesis of novel non-digestible oligosaccharides derived from rare sugars, achieved through transfructosylation of D-tagatose and L-sorbose by levansucrase from Bacillus subtilis CECT 39 (SacB). The characterization of these carbohydrates using NMR and molecular docking was instrumental in elucidating the catalytic mechanism and substrate preference of SacB. Tagatose-based oligosaccharides were higher in abundance than L-sorbose-based oligosaccharides, with the most representative structures being: β-D-Fru-(2→6)-β-D-Fru-(2→1)-D-Tag and β-D-Fru-(2→1)-D-Tag. In vitro studies demonstrated the resistance of tagatose-based oligosaccharides to intestinal digestion and their prebiotic properties, providing insights into their structure-function relationship. β-D-Fru-(2→1)-D-Tag was the most resistant structure to small-intestinal digestion after three hours (99.8% remained unaltered). This disaccharide and the commercial FOS clustered in similar branches, indicating comparable modulatory properties on human fecal microbiota, and exerted a higher bifidogenic effect than unmodified tagatose. The bioconversion of selected rare sugars into β-fructosylated species with a higher degree of polymerization emerges as an efficient strategy to enhance the bioavailability of these carbohydrates and promote their interaction with the gut microbiota. These findings open up new opportunities for tailoring natural rare sugars, like D-tagatose and L-sorbose, to produce novel biosynthesized carbohydrates with functional and structural properties desirable for use as emerging prebiotics and low-calorie sweeteners.

Drude2019IDPC polarizable force field reveals structure-function relationship of insulin

Intrinsically disordered proteins (IDPs) lack stable tertiary structures under physiological conditions, yet play key roles in biological processes and associated with human complex diseases. Their conformational characteristics and high content of charged residues make the use of polarizable force fields an advantageous for simulating IDPs. The Drude2019IDP polarizable force field, previously introduced, has demonstrated comprehensive enhancements and improvements in dipeptides, short peptides, and IDPs, achieving a balanced sampling between IDPs and structured proteins. However, the performance in simulating 5 dipeptides was found to be underestimate. Therefore, we individually performed reweighting and grid-based energy correction map (CMAP) optimization for these 5 dipeptides, resulting in the enhanced Drude2019IDPC force field. The performance of Drude2019IDPC was evaluated with 5 dipeptides, 5 disordered short peptides, and a representative IDP. The results demonstrated a marked improvement comparing with original Drude2019IDP. To further substantiate the capabilities of Drude2019IDPC, MD simulation and Markov state model (MSM) were applied to wild type and mutant for insulin, to elucidate the difference of conformational characteristics and transition path. The findings reveal that mutation can maintain the monomorphic characteristics, providing insights for engineered insulin development. These results indicate that Drude2019IDPC could be used to reveal the structure-function relationship for other proteins.

Investigating the antifungal potential of genetically modified hybrid chitinase enzymes derived from Bacillus subtilis and Serratia marcescens.

Chitinases are glycosyl hydrolase enzymes that break down chitin, an integral component of fungal cell walls. Bacteria such as Bacillus subtilis and Serratia marcescens produce chitinases with antifungal properties. In this study, we aimed to generate hybrid chitinase enzymes with enhanced antifungal activity by combining functional domains from native chitinases produced by B. subtilis and S. marcescens. Chitinase genes were cloned from both bacteria and fused together using overlap extension PCR. The hybrid constructs were expressed in E. coli and the recombinant enzymes purified. Gel electrophoresis and computational analysis confirmed the molecular weights and isoelectric points of the hybrid chitinases were intermediate between the parental enzymes. Antifungal assays demonstrated that the hybrid chitinases inhibited growth of the fungus Fusarium oxysporum significantly more than the native enzymes and also showed fungicidal activity against Candida albicans, Alternaria solani, and Rhizoctonia solani. The results indicate that hybrid bacterial chitinases are a promising approach to engineer novel antifungal proteins. This study provides insight into structure-function relationships of chitinases and strategies for generating biotherapeutics with enhanced bioactive properties. These hybrid chitinases result in a more potent and versatile antifungal agent.

Structural determinants of tendon multiscale mechanics and their sensitivity to mechanical stimulation during development in an embryonic chick model

There is an abrupt increase in the multiscale mechanical properties and load-bearing capabilities of tendon during development. While prior work has identified numerous changes that occur within the collagenous structure during this developmental period, the primary structural elements that give rise to this abrupt increase in mechanical functionality, and their mechanobiological sensitivity, remain unclear. To address this knowledge gap, we used a shear lag model along with ultrastructural imaging, biochemical/thermodynamic assays, and multiscale mechanical testing to investigate the dynamic structure-function relationships during late-stage embryonic chick development and to establish their sensitivity to mechanical stimulation. Mechanical testing and modeling suggested that the rapid increase in multiscale mechanics can be explained by increases in fibril length, intrafibrillar crosslinking, and fibril area fraction. To partially test this, we inhibited collagen crosslinking during development and observed a drastic reduction in multiscale mechanical behavior that was explained by a reduction in both fibril modulus and length. Using muscle paralysis to investigate mechanosensitivity, we observed a significantly impaired multiscale mechanical response despite minimal changes in fibril diameter and fibril area fraction. Additionally, the shear lag model found a trend toward lower fibril lengths with paralysis and experimental data found decreased crosslinking and fibril modulus values following flaccid paralysis. Together, these data suggest that both intrafibrillar crosslink formation and fibril elongation are critical to the formation of load-bearing capabilities in tenogenesis and are sensitive to mechanical loading. These findings provide critical insights into the biological and structural mechanisms that give rise to tensile load-bearing soft tissue. Statement of SignificanceDespite prior work investigating the structural and mechanical changes that occur during tendon development, there has not been a comprehensive analysis of how these simultaneous changes in structure and function are connected. In this study, we performed a comprehensive battery of mechanical and structural assessments of embryonic chick tendons and input these data into a shear lag model to estimate the individual importance of each structural change to the tendon mechanical properties. Additionally, we inhibited muscle activity in the embryos to evaluate the impact of mechanical stimulation on these evolving structure-function relationships during tendon development. These data provide insight into the primary structural elements that produce the tensile load-bearing capabilities of tendon, which will inform efforts to produce tissue engineered tendon replacements.

Structure-function of cartilage in osteoarthritis: An ex-vivo correlation analysis between its structural, viscoelastic and frictional properties

Healthy articular cartilage is characterized by extremely low friction and high compressive stiffness. This dual-functionality is tailored by its biphasic structure, whereby a fluid phase interacts with the extracellular matrix. Osteoarthritis (OA) causes structural changes, thereby altering the biomechanical and frictional properties. How the structural and functional properties of human cartilage are associated with OA remain unknown. To address this, we identified relationships between structural parameters, viscoelastic and frictional properties of degenerated human cartilage through correlation analyses. We found that cartilage friction was mainly influenced by its microscopic structure, while the viscoelastic properties were also related to the macroscopic structure. The viscoelastic and frictional properties displayed a weak correlation. These findings provide insights into the interplay between cartilage structure and its functional properties in OA, which might provide a basis for advancements in diagnosing and treating degenerated human cartilage. Statement of significanceOsteoarthritis causes changes in the cartilages biphasic structure, thereby affecting functionality by altered biomechanical and frictional properties. Currently a cartilage-preserving therapeutic option remains lacking, because the disease is not fully understood. In our correlation analyses, we investigated relationships between the structural, the viscoelastic and frictional properties of degenerated human cartilage. We found that cartilage friction was particularly dependent on the microscopic structure, while the viscoelastic properties also correlated with the macroscopic structure. The frictional properties displayed only a weak dependency with the viscoelastic properties. These new insights into the structure-function and inter-functional relationships may provide new options to advance the diagnosis and treatment of degenerated cartilage.