DOCSLIB.ORG

Change in Collagen Fibril Diameter Distribution of Bovine Anterior Cruciate Ligament Upon Injury Can Be Mimicked in a Nanostructured Scaffold

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Change in Collagen Fibril Diameter Distribution of Bovine Anterior Cruciate Ligament Upon Injury Can Be Mimicked in a Nanostructured Scaffold molecules Article Change in Collagen Fibril Diameter Distribution of Bovine Anterior Cruciate Ligament upon Injury Can Be Mimicked in a Nanostructured Scaffold Zhuldyz Beisbayeva 1, Ainur Zhanbassynova 1, Gulzada Kulzhanova 2, Fariza Mukasheva 1 and Cevat Erisken 1,* 1 Department of Chemical and Materials Engineering, School of Engineering & Digital Sciences, Nazarbayev University, 53 Kabanbay Batyr, Nur-Sultan 010000, Kazakhstan; [email protected] (Z.B.); [email protected] (A.Z.); [email protected] (F.M.) 2 Department of Biological Sciences, Nazarbayev University, 53 Kabanbay Batyr, Nur-Sultan 010000, Kazakhstan; [email protected] * Correspondence: [email protected] Abstract: More than 200,000 people are suffering from Anterior Cruciate Ligament (ACL) related injuries each year in the US. There is an unmet clinical demand for improving biological attachment between grafts and the host tissue in addition to providing mechanical support. For biological graft integration, it is important to provide a physiologically feasible environment for the host cells to enable them to perform their duties. However, behavior of cells during ACL healing and the mechanism of ACL healing is not fully understood partly due to the absence of appropriate environ- ment to test cell behavior both in vitro and in vivo. This study aims at (i) investigating the change Citation: Beisbayeva, Z.; in fibril diameter of bovine ACL tissue upon injury and (ii) fabricating nanofiber-based scaffolds Zhanbassynova, A.; Kulzhanova, G.; to represent the morphology and structure of healthy and injured ACL tissues. We hypothesized Mukasheva, F.; Erisken, C. Change in that distribution and mean diameter of ACL fibrils will be altered upon injury. Findings revealed Collagen Fibril Diameter Distribution of Bovine Anterior Cruciate Ligament that the collagen fibril diameter distribution of bovine ACL changed from bimodal to unimodal upon Injury Can Be Mimicked in a upon injury with subsequent decrease in mean diameter. Polycaprolactone (PCL) scaffold fiber Nanostructured Scaffold. Molecules diameter distribution exhibited similar bimodal and unimodal distribution behavior to qualitatively 2021, 26, 1204. https://doi.org/ represent the cases of healthy and injured ACL, respectively. The native ACL tissue demonstrated 10.3390/molecules26051204 comparable modulus values only with the aligned bimodal PCL scaffolds. There was significant difference between mechanical properties of aligned bimodal and unaligned unimodal PCL scaffolds. Academic Editor: We believe that the results obtained from measurements of diameter of collagen fibrils of native Matthias Schnabelrauch bovine ACL tissue can serve as a benchmark for scaffold design. Received: 20 January 2021 Keywords: injury; anterior cruciate ligament; bovine; collagen; fibril; diameter Accepted: 2 February 2021 Published: 24 February 2021 Publisher’s Note: MDPI stays neutral 1. Introduction with regard to jurisdictional claims in published maps and institutional affil- Anterior cruciate ligament (ACL) injuries have an estimated annual incidence of iations. more than 200,000 in the United States alone [1]. ACL injuries cannot regenerate but heal slowly, resulting in scar tissue formation due to their poorly vascularized nature and frequency of motion. Unfortunately, currently available clinical procedures are not able to fully repair ACL injuries, mainly because of the absence of biological integration between grafts and the host tissue [2]. Reports reveal that females carry three to five times Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. higher risk [3] and that more than one-third of the people with injured ligament tissue This article is an open access article undergo reconstruction surgery each year [1], with an estimated annual cost of more than distributed under the terms and 4 billion dollars for nonsurgical management of ACL injuries, and about 3 billion dollars conditions of the Creative Commons for surgical reconstruction of ACL [4]. Obviously, increased ACL loading stretches the Attribution (CC BY) license (https:// collagen bundles/fibers, a major constituent of the tissue, until partial or complete ligament creativecommons.org/licenses/by/ rupture occurs as a result of disruption of individual collagen fibrils [5–7]. A schematic of 4.0/). the ACL injury is given in Figure1. Molecules 2021, 26, 1204. https://doi.org/10.3390/molecules26051204 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 19 complete ligament rupture occurs as a result of disruption of individual collagen fibrils Molecules 2021, 26, 1204 2 of 17 [5–7]. A schematic of the ACL injury is given in Figure 1. Figure 1. Schematic of a torn/ruptured anterior cruciate ligament (ACL) tissue. Figure 1. Schematic of a torn/ruptured anterior cruciate ligament (ACL) tissue. Structurally, ACL is a poorly vascularized connective tissue composed mainly of elastin,Structurally, glycoproteins, ACL is glycosaminoglycans,a poorly vascularized and connective aligned collagentissue composed fibers (mostly mainly type of I) elastin,surrounded glycoproteins, by fibroblast glycosaminoglycans, cells. It connects and the aligned femur andcollagen tibia fibers with a (mostly basic function type I) of surroundedstabilizing by the fibroblast knee joint cells. through It connects resisting the anterior femur tibialand tibia translation with a andbasic rotational function loads. of stabilizingDuthon the et al. knee reported joint through on the anatomical resisting anterior structure tibial and translation properties and of the rotational ACL in loads. a review Duthonstudy et [8 al.]. Their reported report on defines the anatomical the cross-section structure of and the humanproperties ACL of as the an ACL irregular in a review geometry, studyhaving [8]. anTheir area report of approximately defines the 34 cross mm‐2sectionat the femurof the and human 42 mm ACL2 at theas an tibia irregular junctions. geometry,ACL is composedhaving an area of small of approximately entities called 34 fascicles, mm2 at whichthe femur contain and fibrils42 mm and2 at the fibroblasts. tibia junctions.Fibrils withACL diametersis composed of upof small to 500 entities nm are called formed fascicles, from subfibrils, which contain and consequentlyfibrils and fibroblasts.form microfibrils. Fibrils with diameters of up to 500 nm are formed from subfibrils, and consequentlyFibroblasts form microfibrils. are ligament cells that produce components of the tissue extracellular matrixFibroblasts (ECM) are and ligament form about cells 20% that of totalproduce tissue components volume. The of remaining the tissue proportion extracellular is the matrixECM, (ECM) which and in turn form contains about 60–80%20% of total water. tissue Collagens, volume. mainly The typesremaining I and proportion III, form 70–80% is theof ECM, the dry which volume in turn of the contains ligament 60–80% [9]. A water. summary Collagens, of ACL mainly tissue composition types I and isIII, provided form 70–80%in Table of 1the. dry volume of the ligament [9]. A summary of ACL tissue composition is provided in Table 1. Table 1. Typical composition of ACL tissue [9]. Table 1. Typical composition of ACL tissue [9]. Cellular Materials (20%) Extracellular Materials (80%) Cellular Materials Water (60–80%)Extracellular Materials (80%) Solids (20–40%) (20%) Collagen 70–80% Elastin Fibroblasts Water (60–80%) Solids (20–40%) CollagenType 70–80% I—90% Elastin Fibroblasts Type I—90%Type III—10% Type III—10% ACL composition and structure are distorted upon injury, and its function is thus compromisedACL composition as indicated and structure by inferior are mechanical distorted upon properties. injury, The and arrangement its function of is collagen thus compromisedfibers in ACL as tissue indicated plays aby key inferior role in loadmechanical distribution properties. since wavy The parallel arrangement arrangement of collagenof fibrils fibers provides in ACL mechanical tissue plays resistance a key to role tension in load force distribution along the fiber since axis. wavy During parallel tensile arrangementstretch, a small of fibrils part provides of exerted mechanical load on ACL resistance first flattens to tension the crimp force fibers, along while the fiber application axis. Duringof additional tensile stretch, load stretches a small thepart flattened of exerted fibers load [8 on]. The ACL mechanical first flattens properties the crimp of fibers, ACL are whiledirectly application related toof ultrastructureadditional load of collagenstretches fibers, the flattened therefore fibers an irregular [8]. The arrangement mechanical of propertiescollagen of fibers ACL in are ACL directly can lead related to decreased to ultrastructure mechanical of resistance collagen fibers, to the load,therefore leading an to irregularligament arrangement rupture. In thisof collagen regard, diameter fibers in and ACL density can oflead collagens to decreased are critical mechanical attributes of ACL because they ultimately determine mechanical strength of the tissue [10]. Previously published studies about the dependence of mechanical properties on fibril diameter state that proper functioning of ACL requires multimodal distribution of fibril diameter [9]. In such an arrangement, collagen fibrils with smaller diameters are packed into the voids Molecules 2021, 26, 1204 3 of 17 generated by packing of larger fibrils, thus increasing the packing density reflected into increased mechanical
Load more

Recommended publications
  • Measurement of Collagen Fibril Size and Organization by Electron
    Using transmission electron microscopy and 3View® to determine collagen fibril size and three-dimensional organization Tobias Starborg1,2+, Nicholas S. Kalson1,2+, Yinhui Lu1,2+, Aleksandr Mironov2, Timothy F. Cootes3, David F. Holmes1,2* and Karl E. Kadler1,2* 1Wellcome Trust Centre for Cell-Matrix Research and Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT UNITED KINGDOM 2Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT UNITED KINGDOM 3Faculty of Medicine and Human Sciences, Imaging Sciences and Biomedical Imaging Institute, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT UNITED KINGDOM +Equal contribution *Authors for correspondence: [email protected] [email protected] Telephone +44 161 275 5086 Running title: Size and organization of collagen fibrils in vivo Collagen fibrils are the major tensile element in vertebrate tissues where they occur as ordered bundles in the extracellular matrix. Abnormal fibril assembly and organization results in scarring, fibrosis, poor wound healing and connective tissue diseases. Transmission electron microscopy (TEM) is used to assess formation of the fibrils, predominantly by measuring fibril diameter. Here we describe an enhanced protocol for measuring fibril diameter as well as fibril-volume-fraction, mean fibril length, fibril cross-sectional shape, and fibril 3D organization that are also major determinants of tissue function. Serial section TEM (ssTEM) has been used to visualize fibril 3D-organization in vivo. However, serial block face- scanning electron microscopy (SBF-SEM) has emerged as a time-efficient alternative to ssTEM. The protocol described below is suitable for preparing tissues for TEM and SBF- SEM (by 3View®).
    [Show full text]
  • Recent Developments in Alternative Extraction Processes of Keratin from Keratinous Animal Body Parts As Active Ingredient for Hair Care Products
    J Cosmo Trichol Volume 7:3, 2021 Journal of Cosmetology & Trichology 10.4172/2167-7700.1000263 Review Article Open Access Recent Developments in Alternative Extraction Processes of Keratin from Keratinous Animal Body Parts as Active Ingredient for Hair care Products Ken Tasaki* Division of Upcycling, Tomorrow Water, 1225 N Patt St., Anaheim, CA 92801, United States Abstract Recently, keratin has been attracting intense attentions as an active ingredient for hair care products, given its unique nature such as rejuvenating and anti- aging characteristics. Conventionally, keratin is extracted from keratinous animal body parts (KABPs) such as wool by chemical processes or in combination with enzymes. However, for extraction of keratin from KABPs requires large volumes of highly concentrated toxic chemicals, which is not environmentally sustainable. The time-consuming processes for the extraction and the removal of chemicals slow down the productivity. Lately, a number of alternative extraction processes have been reported. We will review these processes and examine their commercial viability. We also report the recent development in our alternative process based on thermal hydrolysis. Keywords: Keratin • Thermal hydrolysis • Molecular weight distribution • Cystine • Hair care they are eventually decomposed overtime, generating methane emissions. Introduction Recently, valorization of these animal body wastes is receiving intense research [1-4]. With the growing global demand for meats, generation Keratin has been increasingly used as an active ingredient for haircare of KABPs will only increase, ensuring a stable supply of KABPs as raw and skincare products. It is also known to have rejuvenating and anti-aging materials to whatever they are turned into. Currently, cosmetics and effects on hair and skin.
    [Show full text]
  • New Model for Stacking Monomers in Filamentous Actin from Skeletal Muscles of Oryctolagus Cuniculus
    International Journal of Molecular Sciences Article New Model for Stacking Monomers in Filamentous Actin from Skeletal Muscles of Oryctolagus cuniculus Anna V. Glyakina 1,2, Alexey K. Surin 1,3,4, Sergei Yu. Grishin 1 , Olga M. Selivanova 1, Mariya Yu. Suvorina 1, Liya G. Bobyleva 5, Ivan M. Vikhlyantsev 5 and Oxana V. Galzitskaya 1,5,* 1 Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia; [email protected] (A.V.G.); [email protected] (A.K.S.); [email protected] (S.Y.G.); [email protected] (O.M.S.); [email protected] (M.Y.S.) 2 Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia 3 The Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia 4 State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Moscow Region, Russia 5 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia; [email protected] (L.G.B.); [email protected] (I.M.V.) * Correspondence: [email protected]; Tel.: +7-903-675-0156 Received: 29 September 2020; Accepted: 3 November 2020; Published: 6 November 2020 Abstract: To date, some scientific evidence (limited proteolysis, mass spectrometry analysis, electron microscopy (EM)) has accumulated, which indicates that the generally accepted model of double-stranded of filamentous actin (F-actin) organization in eukaryotic cells is not the only one. This entails an ambiguous understanding of many of the key cellular processes in which F-actin is involved.
    [Show full text]
  • Collagens—Structure, Function, and Biosynthesis
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of East Anglia digital repository Advanced Drug Delivery Reviews 55 (2003) 1531–1546 www.elsevier.com/locate/addr Collagens—structure, function, and biosynthesis K. Gelsea,E.Po¨schlb, T. Aignera,* a Cartilage Research, Department of Pathology, University of Erlangen-Nu¨rnberg, Krankenhausstr. 8-10, D-91054 Erlangen, Germany b Department of Experimental Medicine I, University of Erlangen-Nu¨rnberg, 91054 Erlangen, Germany Received 20 January 2003; accepted 26 August 2003 Abstract The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified so far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. This review focuses on the distribution and function of various collagen types in different tissues. It introduces their basic structural subunits and points out major steps in the biosynthesis and supramolecular processing of fibrillar collagens as prototypical members of this protein family. A final outlook indicates the importance of different collagen types not only for the understanding of collagen-related diseases, but also as a basis for the therapeutical use of members of this protein family discussed in other chapters of this issue. D 2003 Elsevier B.V. All rights reserved. Keywords: Collagen; Extracellular matrix; Fibrillogenesis; Connective tissue Contents 1. Collagens—general introduction ............................................. 1532 2. Collagens—the basic structural module.........................................
    [Show full text]
  • Chapter 8: Fibrous Proteins
    ChapterChapter 8:8: FibrousFibrous ProteinsProteins VoetVoet && Voet:Voet: PagesPages 231-240231-240 Lecture 11 Biochemistry 3100 Slide 1 FibrousFibrous ProteinsProteins Fibrous proteins are highly elongated polypeptides composed of a single secondary structure element Primary component of skin, tendon, bone, connective tissues, etc Function as structural material that have protective, connective or supportive roles Simplicity of structure makes relation between structure and function relatively obvious Rarely crystallize (also difficult for NMR) so structural information a variety of indirect techniques Lecture 11 Biochemistry 3100 Slide 2 KeratinsKeratins Mechanically durable and unreactive protein of vertebrates up to 85% of protein in horns, hair, nails & feathers a-keratins occur in mammals; b-keratins occur in birds and reptiles > 30 keratin genes expressed in mammals a-keratins are classified as relatively acidic (Type I) or basic (Type II) Keratins have complex quaternary structures (a) keratins are dimers composed of a Type I and Type II subunit (b) many dimers associate to form protofilaments (c) protofilaments dimerize to form protofibrils (d) protofibrils form tetramers called microfibrils (e) microfibrils associate into macrofibrils Lecture 11 Biochemistry 3100 Slide 3 KeratinKeratin QuaternaryQuaternary StructureStructure Lecture 11 Biochemistry 3100 Slide 4 aa-Keratin-Keratin StructureStructure X-ray scattering and diffraction studies indicate a- keratin has a helical structure with a 5.1 Å pitch (distance per turn of helix)
    [Show full text]
  • Implications for Hard A-Keratin Intermediate Filament M
    Biophysical Journal Volume 82 April 2002 2265–2274 2265 A New Deformation Model of Hard ␣-Keratin Fibers at the Nanometer Scale: Implications for Hard ␣-Keratin Intermediate Filament Mechanical Properties L. Kreplak,* A. Franbourg,† F. Briki,* F. Leroy,† D. Dalle´,‡ and J. Doucet* *Laboratoire pour l’Utilisation du Rayonnement Electromagne´tique (LURE), Baˆt 209D, Centre Universitaire Paris-Sud, 91898 Orsay Cedex, †L’Oreal Recherche, 92583 Clichy Cedex, and ‡Laboratoire de Physique des Solides (LPS), Baˆt 510, Centre Universitaire Paris-Sud, 91405 Orsay Cedex, France ABSTRACT The mechanical behavior of human hair fibers is determined by the interactions between keratin proteins structured into microfibrils (hard ␣-keratin intermediate filaments), a protein sulfur-rich matrix (intermediate filaments asso- ciated proteins), and water molecules. The structure of the microfibril-matrix assembly has already been fully characterized using electron microscopy and small-angle x-ray scattering on unstressed fibers. However, these results give only a static image of this assembly. To observe and characterize the deformation of the microfibrils and of the matrix, we have carried out time-resolved small-angle x-ray microdiffraction experiments on human hair fibers stretched at 45% relative humidity and in water. Three structural parameters were monitored and quantified: the 6.7-nm meridian arc, which is related to an axial separation between groups of molecules along the microfibrils, the microfibril’s radius, and the packing distance between microfibrils. Using a surface lattice model of the microfibril, we have described its deformation as a combination of a sliding process and a molecular stretching process. The radial contraction of the matrix is also emphasized, reinforcing the hydrophilic gel nature hypothesis.
    [Show full text]
  • Corneal Collagen Fibril Structure in Three Dimensions: Structural Insights Into Fibril Assembly, Mechanical Properties, and Tissue Organization
    Corneal collagen fibril structure in three dimensions: Structural insights into fibril assembly, mechanical properties, and tissue organization David F. Holmes*, Christopher J. Gilpin*, Clair Baldock*, Ulrike Ziese†, Abraham J. Koster†, and Karl E. Kadler*‡ *Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Stopford Building 2.205, Oxford Road, Manchester M13 9PT, United Kingdom; and †Department of Molecular Cell Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands Communicated by Darwin J. Prockop, Tulane University, New Orleans, LA, March 26, 2001 (received for review November 3, 2000) The ability of the cornea to transmit light while being mechanically substructure or a crystalline packing of collagen molecules in a resilient is directly attributable to the formation of an extracellular sheet structure (3–5). A five-stranded microfibrillar model was matrix containing orthogonal sheets of collagen fibrils. The de- proposed originally by Smith (6) and then developed by Piez and tailed structure of the fibrils and how this structure underpins the Trus (7, 8) on the basis of sequence regularities and x-ray mechanical properties and organization of the cornea is under- diffraction data. Recent analysis of synchrotron x-ray diffraction stood poorly. In this study, we used automated electron tomog- from rat tail tendon has yielded the best agreement with a raphy to study the three-dimensional organization of molecules in microfibril substructure (9). corneal collagen fibrils. The reconstructions show that the collagen Corneal collagen fibrils are heterotypic structures composed molecules in the 36-nm diameter collagen fibrils are organized into of type I collagen molecules coassembled along with those of microfibrils (Ϸ4-nm diameter) that are tilted by Ϸ15° to the fibril type V collagen (10).
    [Show full text]
  • Energy Dissipation in Mammalian Collagen Fibrils
    Acta Biomaterialia 80 (2018) 217–227 Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat Full length article Energy dissipation in mammalian collagen fibrils: Cyclic strain-induced damping, toughening, and strengthening Julia Liu a, Debashish Das a, Fan Yang a, Andrea G. Schwartz b, Guy M. Genin c,d, Stavros Thomopoulos e, ⇑ Ioannis Chasiotis a, a Aerospace Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA b Orthopaedic Surgery, Washington University, St. Louis, MO 60613, USA c Mechanical Engineering and Materials Science, Washington University, St. Louis, MO 63130, USA d NSF Science and Technology Center for Engineering Mechanobiology, St. Louis, MO 63130, USA e Orthopedic Surgery, Biomedical Engineering, Columbia University, New York, NY 10032, USA article info abstract Article history: As the fundamental structural protein in mammals, collagen transmits cyclic forces that are necessary for Received 1 April 2018 the mechanical function of tissues, such as bone and tendon. Although the tissue-level mechanical behav- Received in revised form 29 August 2018 ior of collagenous tissues is well understood, the response of collagen at the nanometer length scales to Accepted 17 September 2018 cyclical loading remains elusive. To address this major gap, we cyclically stretched individual reconsti- Available online 19 September 2018 tuted collagen fibrils, with average diameter of 145 ± 42 nm, to small and large strains in the partially hydrated conditions of 60% relative humidity. It is shown that cyclical loading results in large steady- Keywords: state hysteresis that is reached immediately after the first loading cycle, followed thereafter by limited Hysteresis accumulation of inelastic strain and constant initial elastic modulus.
    [Show full text]
  • Mechanical Behavior of Individual Type I Collagen Fibrils
    MECHANICAL BEHAVIOR OF INDIVIDUAL TYPE I COLLAGEN FIBRILS BY JULIA HONG LIU THESIS Submitted in partial fulfillment of the requirements for the degree of Master of Science in Aerospace Engineering in the Graduate College of the University of Illinois at Urbana-Champaign, 2016 Urbana, Illinois Adviser: Professor Ioannis Chasiotis ABSTRACT Despite the plethora of studies on the mechanical response of collagen, especially at the molecular scale or at much larger length scales, such as of those of fibers, tendons, and fascicles, there is still limited information about the mechanics of collagen fibrils (50 - 500 nm diameter) that serve as mesoscale building blocks in tissues. In this dissertation research the mechanical behavior of dry individual reconstituted collagen fibrils with different diameters were investigated via monotonic tests at 0.004 s-1, cyclic loading and cyclic loading/recovery experiments, and strain rate tests spanning six decades of strain rates in the range 10-3 – 102 s-1. Experiments were conducted with reconstituted type I calfskin collagen fibrils which were isolated from buffer and after drying were adhesively attached to a microelectromechanical systems (MEMS) device. Experiments were carried out using high-resolution optical microscopy under dry conditions at 20-30% relative humidity (RH) and laboratory temperature. Eight fibrils with diameters of 165±77 nm tested under monotonic loading yielded an average tensile strength of 752±186 MPa, ultimate stretch ratio of 1.3±0.06, and initial stiffness of the stress (σ) vs. stretch ratio (λ) curves, E1 = 5.7±2.3 GPa. These results depended on fibril diameter: fibrils with larger diameters showed increased maximum stretch ratio, λmax, and decreased E1 and decreased stiffness, E2, of the softening regime in the σ - λ curves.
    [Show full text]
  • Mechanical Model for a Collagen Fibril Pair in Extracellular Matrix
    Mechanical model for a collagen fibril pair in extra cellular matrix Chan Y.1, Cox G.M.1, Haverkamp R.G.2, Hill J.M.1 1 Nanomechanics Group, School of Mathematics and Applied Statistics, University of Wollongong, Wollongong, NSW, 2522, Australia 2 Institute of Technology and Engineering, Massey University, Palmerston North 5331, New Zealand October 26, 2018 Abstract In this paper, we model the mechanics of a collagen pair in the connective tissue extracellular matrix that exists in abundance throughout animals, including the human body. This connective tissue comprises repeated units of two main structures, namely collagens as well as axial, parallel and regular anionic glycosaminoglycan between collagens. The collagen fibril can be modeled by Hooke’s law whereas anionic glycosaminoglycan behaves more like a rubber-band rod and as such can be better modeled by the worm-like chain model. While both computer simulations and continuum mechanics models have been investigated the behavior of this connective tissue typically, authors either assume a simple form of the molecular potential energy or entirely ignore the microscopic structure of the connective tissue. Here, we apply basic physical methodologies and simple applied mathematical modeling techniques to describe the collagen pair quantitatively. We find that the growth of fibrils is intimately related to the maximum length of the anionic glycosaminoglycan and the relative displacement of two adjacent fibrils, which in return is closely related to the effectiveness of anionic glycosaminoglycan in transmitting forces between fibrils. These reveal the importance of the anionic glycosaminoglycan in maintaining the structural shape of the connective tissue extracellular matrix and eventually the shape modulus of human tissues.
    [Show full text]
  • Mechanisms of Amyloid Fibril Formation by Proteins
    REVIEW ARTICLE Mechanisms of amyloid fibril formation by proteins Santosh Kumar and Jayant B. Udgaonkar* National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560 065, India Understanding the principles of amyloid fibril forma- Understanding the structural heterogeneity inherent in the process of amyloid fibril formation is an impor- tion is an important problem in modern biology. Many tant goal of protein aggregation studies. Structural human diseases, including Alzheimer’s disease, Parkin- heterogeneity in amyloid fibrils formed by a protein son’s disease, Huntington’s disease as well as the prion manifests itself in fibrils varying in internal structure diseases, are associated with the formation of amyloid and external appearance, and may originate from fibrils10. In amyloidoses, amyloid fibrils accumulate in molecular level variations in the internal structure of the brain, or in one or more other tissues11. Amyloid the cross-β motif. Amyloid fibril formation commences fibrils are, however, not always harmful. It is now in- from partially structured conformations of a protein, creasingly being seen that living organisms, ranging from and in many cases, proceeds via pre-fibrillar aggre- prokaryotes to humans, exploit amyloid fibrils formed by gates (spherical oligomers and/or protofibrils). It now their endogenous proteins for carrying out normal physio- appears that structural heterogeneity is prevalent in logical functions11,12. From the biotechnology perspective, the partially structured conformations as well as in amyloid fibrils also appear promising as macromolecular the pre-fibrillar aggregates of proteins. Amyloid fibril 13–15 formation may therefore potentially commence from assembly based nanomaterials . many precursor states, and amyloid fibril polymor- The term ‘amyloid’ was first used by Rudolf Virchow phism might be the consequence of the utilization of to describe a structured mass in human tissues, which was distinct nucleation and elongation mechanisms.
    [Show full text]
  • Collagen Assembly at the Cell Surface: Dogmas Revisited
    cells Review Collagen Assembly at the Cell Surface: Dogmas Revisited Moses Musiime 1 , Joan Chang 2 , Uwe Hansen 3, Karl E. Kadler 2 ,Cédric Zeltz 1 and Donald Gullberg 1,* 1 Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway; [email protected] (M.M.); [email protected] (C.Z.) 2 Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK; [email protected] (J.C.); [email protected] (K.E.K.) 3 Institute for Musculoskeletal Medicine, University Hospital of Münster, 48149 Münster, Germany; [email protected] * Correspondence: [email protected]; Tel.: +47-9280-4941 Abstract: With the increased awareness about the importance of the composition, organization, and stiffness of the extracellular matrix (ECM) for tissue homeostasis, there is a renewed need to understand the details of how cells recognize, assemble and remodel the ECM during dynamic tissue reorganization events. Fibronectin (FN) and fibrillar collagens are major proteins in the ECM of interstitial matrices. Whereas FN is abundant in cell culture studies, it is often only transiently expressed in the acute phase of wound healing and tissue regeneration, by contrast fibrillar collagens form a persistent robust scaffold in healing and regenerating tissues. Historically fibrillar collagens in interstitial matrices were seen merely as structural building blocks. Cell anchorage to the collagen matrix was thought to be indirect and occurring via proteins like FN and cell surface-mediated collagen fibrillogenesis was believed to require a FN matrix.
    [Show full text]