Collagen Network Architecture Varies Between Pure Collagen and Collagen-Fibrin Co-Gels

2012 ◽  
Author(s):  
Victor K. Lai ◽  
Allan M. Kerandi ◽  
Spencer P. Lake ◽  
Robert T. Tranquillo ◽  
Victor H. Barocas
Keyword(s):  
Mechanical Behavior ◽  
Network Architecture ◽  
Rational Design ◽  
Structural Integrity ◽  
Collagen Network ◽  
Fibrin Gel ◽  
Ecm Proteins ◽  
Fibrin Networks ◽  
Pure Collagen ◽  
Function Relationship

Naturally-occurring extracellular matrix (ECM) proteins, e.g. collagen I and fibrin, play an important role in tissues, conferring structural integrity and providing a biochemical environment for eliciting important cellular responses (e.g. migration). Tissue engineers use a variety of matrix polymers as initial scaffolds for seeding cells, sometimes in combination with one another (e.g. collagen-fibrin [1]). For example, our group fabricates arterial tissue equivalents (TEs) by seeding cells in a fibrin gel, which is gradually degraded over time and replaced by cell-produced collagen [2]. While the structure and mechanics of individual ECM proteins have been studied extensively, how multiple fibrillar networks interact to confer overall mechanical behavior remains poorly understood. Narrowing this gap in knowledge of scaffolds comprising multiple fibril networks is crucial in allowing for more rational design in tissue engineering, as cells react differently according to their mechanical environments. For collagen-fibrin networks in particular, early efforts in elucidating interactions between these two fibril networks in co-gels have proven inconclusive due to inconsistent findings from various groups. Recent modeling efforts by our group have shown that simple “series” and “parallel” type interactions provide bounds for the mechanical behavior of collagen-fibrin co-gels [3]. In addition, experiments on pure collagen and fibrin vs. their respective networks from collagen-fibrin co-gels after digestion showed slight differences in mechanical behavior [4]. These previous studies have focused on the composition-function relationship between collagen and fibrin. The objective of the current work is to explore how collagen network architecture changes in the presence of the fibrin network in collagen-fibrin co-gels, thereby providing an added dimension to our understanding of collagen-fibrin systems by elucidating structure-composition-function relationships between collagen and fibrin.

scholarly journals Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

2021 ◽  
Vol 22 (11) ◽  
pp. 5989
Author(s):  
Bilal Ahmad ◽  
Maria Batool ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Rational Design ◽  
Structural Integrity ◽  
Critical Role ◽  
Autoimmune Encephalitis ◽  
Affinity Maturation ◽  
Antibody Binding ◽  
Computational Techniques ◽  
Multiple Strategies ◽  
Binding Epitope

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.

scholarly journals Vision and Deep Learning-Based Algorithms to Detect and Quantify Cracks on Concrete Surfaces from UAV Videos

Sensors ◽  
2020 ◽  
Vol 20 (21) ◽  
pp. 6299 ◽  
Author(s):  
Sutanu Bhowmick ◽  
Satish Nagarajaiah ◽  
Ashok Veeraraghavan
Keyword(s):  
Image Segmentation ◽  
Deep Learning ◽  
Network Architecture ◽  
Structural Integrity ◽  
Real Life ◽  
Concrete Surface ◽  
Video Camera ◽  
Bending Test ◽  
Morphological Operations ◽  
Civil Infrastructures

Immediate assessment of structural integrity of important civil infrastructures, like bridges, hospitals, or dams, is of utmost importance after natural disasters. Currently, inspection is performed manually by engineers who look for local damages and their extent on significant locations of the structure to understand its implication on its global stability. However, the whole process is time-consuming and prone to human errors. Due to their size and extent, some regions of civil structures are hard to gain access for manual inspection. In such situations, a vision-based system of Unmanned Aerial Vehicles (UAVs) programmed with Artificial Intelligence algorithms may be an effective alternative to carry out a health assessment of civil infrastructures in a timely manner. This paper proposes a framework of achieving the above-mentioned goal using computer vision and deep learning algorithms for detection of cracks on the concrete surface from its image by carrying out image segmentation of pixels, i.e., classification of pixels in an image of the concrete surface and whether it belongs to cracks or not. The image segmentation or dense pixel level classification is carried out using a deep neural network architecture named U-Net. Further, morphological operations on the segmented images result in dense measurements of crack geometry, like length, width, area, and crack orientation for individual cracks present in the image. The efficacy and robustness of the proposed method as a viable real-life application was validated by carrying out a laboratory experiment of a four-point bending test on an 8-foot-long concrete beam of which the video is recorded using a camera mounted on a UAV-based, as well as a still ground-based, video camera. Detection, quantification, and localization of damage on a civil infrastructure using the proposed framework can directly be used in the prognosis of the structure’s ability to withstand service loads.

scholarly journals RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 925 ◽  
Author(s):  
Marta Szabat ◽  
Dagny Lorent ◽  
Tomasz Czapik ◽  
Maria Tomaszewska ◽  
Elzbieta Kierzek ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rational Design ◽  
Rna Virus ◽  
Viral Rna ◽  
Structure Information ◽  
A Genome ◽  
Function Relationship ◽  
Interfering Rna

Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.

Chlorhexidine Arrests Subclinical Degradation of Dentin Hybrid Layers in vivo

2005 ◽  
Vol 84 (8) ◽  
pp. 741-746 ◽  
Author(s):  
J. Hebling ◽  
D.H. Pashley ◽  
L. Tjäderhane ◽  
F.R. Tay
Keyword(s):  
Null Hypothesis ◽  
Structural Integrity ◽  
Collagen Network ◽  
Collagen Matrices ◽  
Mmp Inhibitor ◽  
Transmission Electron ◽  
Etch And Rinse ◽  
Hybrid Layers ◽  
Phosphoric Acid Etching

The recent paradigm that endogenous collagenolytic and gelatinolytic activities derived from acid-etched dentin result in degradation of hybrid layers requires in vivo validation. This study tested the null hypothesis that there is no difference between the degradation of dentin bonded with an etch-and-rinse adhesive and that in conjunction with chlorhexidine, an MMP inhibitor, applied after phosphoric-acid-etching. Contralateral pairs of bonded Class I restorations in primary molars of clinical subjects were retrieved after a six-month period of intra-oral functioning and processed for transmission electron microscopy. Hybrid layers from the chlorhexidine-treated teeth exhibited normal structural integrity of the collagen network. Conversely, abnormal hybrid layers were seen in the control teeth, with progressive disintegration of the fibrillar network, to the extent that it was beyond detection by collagen staining. Self-destruction of collagen matrices occurs rapidly in resin-infiltrated dentin in vivo and may be arrested with the use of chlorhexidine as an MMP inhibitor.

scholarly journals Connectivity patterns shape sensory representation in a cerebellum-like network

2021 ◽  
Author(s):  
Daniel Zavitz ◽  
Elom A. Amematsro ◽  
Alla Borisyuk ◽  
Sophie J.C. Caron
Keyword(s):  
Learning Outcomes ◽  
Network Architecture ◽  
Mushroom Body ◽  
Structural Features ◽  
Projection Neurons ◽  
Sensory Representation ◽  
Learning Function ◽  
Kenyon Cells ◽  
Connectivity Patterns ◽  
Function Relationship

SUMMARYCerebellum-like structures are found in many brains and share a basic fan-out–fan-in network architecture. How the specific structural features of these networks give rise to their learning function remains largely unknown. To investigate this structure–function relationship, we developed a realistic computational model of an empirically very well-characterized cerebellum-like structure, the Drosophila melanogaster mushroom body. We show how well-defined connectivity patterns between the Kenyon cells, the constituent neurons of the mushroom body, and their input projection neurons enable different functions. First, biases in the likelihoods at which individual projection neurons connect to Kenyon cells allow the mushroom body to prioritize the learning of particular, ethologically meaningful odors. Second, groups of projection neurons connecting preferentially to the same Kenyon cells facilitate the mushroom body generalizing across similar odors. Altogether, our results demonstrate how different connectivity patterns shape the representation space of a cerebellum-like network and impact its learning outcomes.

scholarly journals STRUCTURAL DESIGN PROCEDURES FOR CONCRETE ARMOUR UNITS

1984 ◽  
Vol 1 (19) ◽  
pp. 172 ◽  
Author(s):  
Kevin R. Hall ◽  
W.F. Baird ◽  
D.J. Turcke
Keyword(s):  
Structural Design ◽  
Rational Design ◽  
Structural Integrity ◽  
Design Procedure ◽  
Analytical Techniques ◽  
Structural Performance ◽  
Design Procedures ◽  
Design Loads ◽  
Resultant Stress ◽  
Hydraulic Stability

A rational design procedure for rubblemound breakwater protection which will ensure both the structural integrity and hydraulic stability of individual concrete armour units and the overall armour system is presented. The procedure involves new experimental techniques for measuring strains in model concrete armour units in a hydraulic model of a breakwater subjected to simulated prototype wave attack and analytical techniques for determining equivalent prototype loads on units. Selected design loads are used to define the resultant stress distribution to allow the designer to take the necessary measures to ensure the structural performance of the unit in a breakwater environment•

scholarly journals Sequence-to-structure dependence of isolated IgG Fc complex biantennary N-glycans: A molecular dynamics study

2018 ◽  
Author(s):  
Aoife M Harbison ◽  
Lorna P Brosnan ◽  
Keith Fenlon ◽  
Elisa Fadda
Keyword(s):  
Molecular Dynamics ◽  
Structural Integrity ◽  
Md Simulations ◽  
Structure And Dynamics ◽  
Differential Recognition ◽  
Dependent Cell ◽  
Function Relationship ◽  
Simulation Time ◽  
Core Fucosylation

AbstractFc glycosylation of human immunoglobulins G (IgGs) is essential for their structural integrity and activity. Interestingly, the specific nature of the Fc glycoforms is known to modulate the IgG effector function. Indeed, while core-fucosylation of IgG Fc-glycans greatly affects the antibody-dependent cell-mediated cytotoxicity (ADCC) function, with obvious repercussions in the design of therapeutic antibodies, sialylation can reverse the antibody inflammatory response, and galactosylation levels have been linked to aging, to the onset of inflammation, and to the predisposition to rheumatoid arthritis. Within the framework of a structure-to-function relationship, we have studied the role of the N-glycan sequence on its intrinsic conformational propensity. Here we report the results of a systematic study, based on extensive molecular dynamics (MD) simulations in excess of 62 µs of cumulative simulation time, on the effect of sequence on the structure and dynamics of increasingly larger, complex biantennary N-glycoforms, i.e. from chitobiose to the larger N-glycan species commonly found in the Fc region of human IgGs. Our results show that while core fucosylation and sialylation do not affect the intrinsic dynamics of the isolated (unbound) N-glycans, galactosylation of the α(1-6) arm shifts dramatically its conformational equilibrium from an outstretched to a folded conformation. These findings are in agreement with and can help rationalize recent experimental evidence showing a differential recognition of positional isomers in glycan array data and also the preference of sialyltransferase for the more reachable, outstretched α(1-3) arm in both isolated and Fc-bound N-glycans.

scholarly journals Metal-Free Heptazine-Based Porous Polymeric Network as Highly Efficient Catalyst for CO2 Capture and Conversion

2021 ◽  
Vol 9 ◽  
Author(s):  
Neha Sharma ◽  
Bharat Ugale ◽  
Sunil Kumar ◽  
Kamalakannan Kailasam
Keyword(s):  
Rational Design ◽  
Structural Integrity ◽  
Cycloaddition Reaction ◽  
Value Added ◽  
Cyclic Carbonate ◽  
Energy Crisis ◽  
Water Stability ◽  
High Chemical ◽  
Efficient Catalyst ◽  
Microporous Polymer

The capture and catalytic conversion of CO2 into value-added chemicals is a promising and sustainable approach to tackle the global warming and energy crisis. The nitrogen-rich porous organic polymers are excellent materials for CO2 capture and separation. Herein, we present a nitrogen-rich heptazine-based microporous polymer for the cycloaddition reaction of CO2 with epoxides in the absence of metals and solvents. HMP-TAPA, being rich in the nitrogen site, showed a high CO2 uptake of 106.7 mg/g with an IAST selectivity of 30.79 toward CO2 over N2. Furthermore, HMP-TAPA showed high chemical and water stability without loss of any structural integrity. Besides CO2 sorption, the catalytic activity of HMP-TAPA was checked for the cycloaddition of CO2 and terminal epoxides, resulting in cyclic carbonate with high conversion (98%). They showed remarkable recyclability up to 5 cycles without loss of activity. Overall, this study represents a rare demonstration of the rational design of POPs (HMP-TAPA) for multiple applications.

scholarly journals Fibrin Nanostructures for Biomedical Applications

2016 ◽  
pp. S263-S272 ◽  
Author(s):  
Z. RIEDELOVÁ-REICHELTOVÁ ◽  
E. BRYNDA ◽  
T. RIEDEL
Keyword(s):  
Biomedical Applications ◽  
Heart Valves ◽  
Catalytic Effect ◽  
Antithrombin Iii ◽  
Bioactive Molecules ◽  
Bulk Solution ◽  
Polymerization Time ◽  
Fibrin Gel ◽  
Fibrin Networks ◽  
And Cartilage

Fibrin is a versatile biopolymer that has been extensively used in tissue engineering. In this paper fibrin nanostructures prepared using a technique based on the catalytic effect of fibrin-bound thrombin are presented. This technique enables surface-attached thin fibrin networks to form with precisely regulated morphology without the development of fibrin gel in bulk solution. Moreover, the influence of changing the polymerization time, along with the antithrombin III and heparin concentrations on the morphology of fibrin nanostructures was explored. The binding of bioactive molecules (fibronectin, laminin, collagen, VEGF, bFGF, and heparin) to fibrin nanostructures was confirmed. These nanostructures can be used for the surface modification of artificial biomaterials designed for different biomedical applications (e.g. artificial vessels, stents, heart valves, bone and cartilage constructs, skin grafts, etc.) in order to promote the therapeutic outcome.

Remodeling in Cell-Seeded Fibrin Gels: Changes in Composition, Organization, and Planar Biaxial Mechanical Behavior

2009 ◽  
Author(s):  
Edward A. Sander ◽  
Sandra L. Johnson ◽  
Victor H. Barocas ◽  
Robert T. Tranquillo
Keyword(s):  
Aspect Ratio ◽  
Stress Field ◽  
Mechanical Behavior ◽  
The Other ◽  
Fibrin Gel ◽  
Fiber Alignment ◽  
Mechanical Environment ◽  
Heterogeneous Sample ◽  
Fibrin Gels ◽  
Stress Environment

Engineered tissues are necessary to replace diseased and damaged tissues incapable of healing on their own. One method employed to produce them involves cell entrapment in a fibrin gel constrained by specially designed molds [1]. As the cells compact and remodel the gel, the combination of mold constraints and cell tractions produces fiber alignment similar to native tissues [2]. One potentially important factor in the remodeling outcome is the local mechanical environment that develops during the compaction and remodeling process. It is well established that the global stress environment leads to changes in remodeling in an isotropic sample [3], but we do not know the effect of local variations in stress field in a heterogeneous sample. To begin to assess the local mechanical environment’s role, we examined the remodeling process in cross-shaped Teflon molds (cruciforms). In this experiment, two mold geometries with differing channel widths were examined: a 1:1 aspect ratio in which the both axes possessed 8 mm wide channels, and a 1:0.5 aspect ratio in which one axis had 8 mm wide channels and the other 4 mm wide channels (fig. 1).

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