ECM and Connective Tissue Lecture 2024 PDF

Extracellular Matrix and Connective Tissue Dr Ashik Srinivasan School of Medical Sciences Last edit: 22-Apr-2024 Lecture date: 23-Apr-2024 Thank You: Dr Belal Chami (author of previous version of...

Extracellular Matrix and Connective Tissue Dr Ashik Srinivasan School of Medical Sciences Last edit: 22-Apr-2024 Lecture date: 23-Apr-2024 Thank You: Dr Belal Chami (author of previous version of this lecture) Learning Objectives Identify and describe the constituents of ECMs and relate their properties to structure and function Identify the types of ECM, using examples from different organs/tissues. Describe the process of adaptative/ECM remodeling with respect to various involved proteins.  Extracellular Matrix Most cells are Embedded In ECM ECM – makes up a considerable part of tissue Volume (quite a lot in some tissues, most in some others) ECM composition: Collagen Elastin Glycosaminoglycans – Hyaluronic Acid – Heparan Sulphate Proteoglycans Image from ‘Gray’s Anatomy’, 35th Edn, Longman, 1973 +++……. Example 1: Cartilage http://histology-world.com/photoalbum/displayimage.php?pid=671 Chondrocytes make up only 5-10% of the volume in cartilage >90% of the volume is ECM Cartilage ECM is made of: Type II collagen, an interlocking mesh of fibrous proteins and proteoglycans (PGs), hyaluronic acid (HA), and chondroitin sulfate (CS).  Example 2: Small intestinal mesentery Showing blood vessels, fibroblasts & ECM: Collagen, Elastin Fibres, GAGs Fibroblasts Make Bulk of ECM Image - Ross, Romrell & Kaye, Histology A Text & Atlas, 1995  Example 3: Blood We have recently been looking at the composition of plasma and what it contains…. Plasma is the ECM of the blood ! Image – Southern Illinois University at https://histology.siu.edu/intro/bldcells.htm In a 70kg person, ~ 60% of the body is water = 42 kg water Of this, ~ 60% is intracellular ICF = 25 kg ~ 40% is extracellular ECF= 17 kg Of the ECF, one fifth is intravascular : 3.4 kg of plasma in 6 kg of blood four fifths is extravascular : 13.5 kg of interstitial fluid Approx. that much water is held by the ECM in the extravascular tissues All numbers here are approximations Collagen 25% of all protein Major ECM Protein Rope-like Structures Resist Tension but not compression Image - Ross, Romrell & Kaye, Histology A Text & Atlas, 1995  Collagen fibres are cross-banded in transmission electron micrographs Self Assembly of Preformed Units Triple Helix That Aggregates Image - Ross, Romrell & Kaye, Histology A Text & Atlas, 1995 What separates the collagen fibres? Proteoglycans and hyaluronic acids trapping water https://quizlet.com/ca/298677677/biochemistry-nonenzymatic-protein-function-and-protein-analyses-flash-cards/  Collagen: synthesized intracellularly, matured extracellularly Image – Alberts et al., Molecular Biology of the Cell, 5th Edn, 2008 Oral Submucosal Fibrosis Chronic consumption of the Areca nut – Arecoline: toxic compound Presence of fibrotic bands and blanching of oral mucosa Oral rigidity Presence of fibrotic bands and inflammation Pindborg, Murti, Bhonsle, Gupta, Daftary & MEHTA, 1984 Elastin – ‘Rubber Band x 5’ Similar to Collagen Hydrophobic Uncoiling Domains Image – Alberts et al., Molecular Biology of the Cell, 5th Edn, 2008 Ross, Romrell & Kaye, Histology A Text & Atlas, 1995 Glycosaminoglycans – GAGs (aka mucopolysaccharides) Long Unbranched Polysaccharides All Repeating Disaccharide Units Amino Sugar Uronic Acid Glycosaminoglycans – GAGs All Repeating Disaccharide Units Glycosaminoglycans - GAGs Strong Negative Charge – (Often Sulphated & Carboxyl Groups) Heparan Sulphate Hyaluronic Acid Attract & Trap Water By: – Strong Charge (Water is polar) – Trapping Cations – e.g., sodium, potassium and calcium Provides hydration and swelling pressure to withstand compression forces.  Hyaluronic Acid Formed at Cell Surface by Enzyme Complex Not Sulphated Extremely long chains Scaffold Binding Many Proteoglycans ‘Goo’ molecule Major component of ECM, especially abundant in synovial fluid Image – Alberts et al., Molecular Biology of the Cell, 5th Edn, 2008  Heparan Sulphate Components manufactured in Golgi Similar to hyaluronic acid, except highly sulphated Regulates a wide range of biological activities including angiogenesis, blood coagulation and cellular signalling Image – Alberts et al., Molecular Biology of the Cell, 5th Edn, 2008  Proteoglycans Protein Core with attached GAGs (excl. hyaluronic acid, though can form non-covalent complexes with proteoglycans) Known as the ‘filler’ of ECM space The major biological function of proteoglycans derives from the physicochemical characteristics of GAGs Image – Alberts et al., Molecular Biology of the Cell, 5th Edn, 2008 http://www.amsbio.com/brochures/Proteoglycans.pdf  Predict The Physical Properties of Tissue From Image? Relate Macro- to Micro to Biochemical Image from ‘Gray’s Anatomy’, 35th Edn, Longman, 1973  Cells Bind ECM Via Adhesion Molecules Pemphigus Vulgaris – autoimmune disease Autoantibodies reducing desmosomal adhesion between epithelial cells Image – Alberts et al., Molecular Biology of the Cell, 5th Edn, 2008 ECM in Constant Turnover Permits Remodelling / Adaptation to Function Synthesis Balanced by Degradation Degradation by Enzymes Enzymes Focused in Activity – Often by Cell Receptors Hyaluronidase Proteinases: – Metaloproteinases (MMPs) – Serine Proteinases Matrix Metalloproteinases Dependent on metals as cofactors (Zn, Ca, Mg) Usually secreted as (inactive) pro-enzymes Activated by proteinases (serine) or reactive oxygen species (ROS) Inhibited by Tissue Inhibitors of Metaloproteinases (TIMPs) Examples: Collagenase, Gelatinase, Stromeolysin Serine Proteinases Often Activated by Other Serine Proteinases Not dependent on metals Inhibited by Serpins Examples: Plasminogen, Plasminogen Activators, Trypsin, Many Clotting & Inflammatory Proteinases Connective Tissues Join tissues together Usually have blood vessels (Epithelium never has blood vessels inside of it) Image -Gray’s Anatomy’, 35th Edn, Longman, 1973  Connective Tissues Cells are separated from each other (fibroblasts, adipocytes, mast cells) Extracellular matrix (collagen, elastin, glycosaminoglycan, hyaluronic acid) Blood vessels Image -Gray’s Anatomy’, 35th Edn, Longman, 1973 Connective Tissues Usually have blood vessels Support the organs and other special tissues Fill in spaces Connect tissues together Support the epithelium (lamina propria) Connective Tissues - Types Loose collagenous connective tissue Dense collagenous connective tissue Elastic tissue Bone Cartilage (No blood vessels) Adipose tissue (Fat) Blood  Loose Connective Tissue Whole mount of small intestinal mesentery showing blood vessels, elastin fibres and fibroblasts Image - Ross, Romrell & Kaye, Histology A Text & Atlas, 1995  Dense connective tissue Tendon is a good example of a Dense connective tissue (Dense collagenous connective tissue) Image - Ross, Romrell & Kaye, Histology A Text & Atlas, 1995  Tendons join muscles and bones together Also sometimes form between tissue masses and organs Macroscopically, tendons are white/opaque because they have very few blood vessels and are neatly arranged collagen fibres Lots of collagen fibres - so are very hard and rope-like (collagen arranged in lines) Very similar to scar tissue in appearance and structure  Appearance & Physical Properties of Connective Tissues Summation of: Cellularity Vascularity ECM - Collagen - Elastin - GAGs NOTE: Cells Generally Do Not Compress Image -Gray’s Anatomy’, 35th Edn, Longman, 1973 Adipose Tissue – Special Connective Tissue Triglyceride / H2O Store Structural – Especially Hands, Soles, Orbit – Resist Starvation Body Contour – Sexual Morphology Image - Ross, Romrell & Kaye, Histology A Text & Atlas, 1995 Bone Highly Vascular Calcified Collagen Internal Structure Optimized to Resist Forces (Wolf’s Law) Soft Tissue (Marrow) in spaces Image – Medimage, Sciencephotolibrary  Osteocytes Lamelae Canaliculi Haversian Canals containing Vessels Histology A Text & Atlas., Ross, Romrell & Kay, 3rd Edn Williams & Wilkins, 1995; & DM Walker Osteocytes in Lacunae Lamelae Canaliculi Haversian Canals containing Vessels Histology A Text & Atlas., Ross, Romrell & Kay, 3rd Edn Williams & Wilkins, 1995; & DM Walker Bone Remodellng is Always a Surface Process Key Cells in Bone: Osteoblasts Osteocytes (Trapped osteoblasts) Osteoclasts (Multinucleated, Derived from Monocytes) See you again at 11am for the lecture on Epithelial Tissue… TTFN ☺