BIOL 4210 – Cell and Molecular Biology – Lecture 26 Study Notes
BIOL 4210 – Cell and Molecular Biology – Lecture 26: Extracellular Matrix
Lecture Information
Presented by Dr. David E. Nelson
Contact: david.e.nelson@mtsu.edu
Location: SCI2016
Learning Objectives
Know about the composition of extracellular matrix in animals.
Know about cell-matrix junctions.
Objective 1: Extracellular Matrix (ECM)
Definition: The extracellular matrix (ECM) is a collection of extracellular molecules secreted by cells that provide structural and biochemical support to surrounding cells.
Composition of ECM:
Primarily consists of three major classes of macromolecules:
Proteoglycans and Glycosaminoglycans (GAGs)
Fibrous proteins
Glycoproteins
Image Description:
Illustrated description of the ECM present in connective tissue underlying an epithelium, showing fibroblasts surrounded by collagen fibrils.
The space between the cells and collagen fibrils is filled with glycoproteins, hyaluronan, and proteoglycans, creating a hydrated gel around the cells.
Types of GAGs and Their Roles
Hyaluronan:
Lacks sulfate groups.
Synthesized at the plasma membrane.
Four main groups of GAGs:
Hyaluronan
Chondroitin sulfate and dermatan sulfate
Heparan sulfate
Keratan sulfate
Properties of GAGs:
Rigid polysaccharide chains that do not fold into globular structures.
Highly hydrophilic, adopting extended conformations, which results in the filling of large volumes relative to their mass, effectively forming hydrated gels.
Proteoglycan Structure
Definition: Proteoglycans are composed of GAG chains covalently linked to a core protein.
Structure:
Except for hyaluronan, all GAGs are covalently attached to proteins, forming proteoglycans through a link tetrasaccharide.
Examples of Proteoglycans:
Decorin: A small proteoglycan consisting of a short core protein with a GAG linked.
Aggrecan: Composed of a serine-rich core protein with approximately 100 chondroitin sulfate chains and about 30 keratan sulfate chains.
Aggrecan Aggregates: Formed from non-covalent attachments of aggrecans to hyaluronan, which can reach massive sizes (~$10^8$ daltons), similar in volume to bacterial cells, and constitute part of the matrix of cartilage.
Collagen Structure and Types
Collagen:
Major fibrous proteins in the ECM characterized by a primary sequence where glycine appears at every 3rd amino acid; other amino acids (X and Y) are often proline and hydroxyproline.
Collagen Triple Helix: Collagen molecules pack together in a triple helix structure.
Types of Collagen and Their Properties:
Table 19-2 Summary:
Type I: Fibril-forming; predominant in bone, skin, tendons; accounts for 90% of body collagen.
Type II: Found in cartilage, intervertebral discs.
Type III: Found in skin, blood vessels, internal organs.
Type IV: Network-forming; forms a sheet-like structure in the basal lamina.
Clinical Implications:
Mutations in collagen types can cause various phenotypes, including severe skin blistering or conditions like osteogenesis imperfecta (brittle bone disease) and Ehlers-Danlos syndrome (loose joints, fragile skin).
Elastin and Its Characteristics
Elastin:
Forms a network of cross-linked molecules, allowing it to stretch and recoil like a rubber band.
Coated with microfibrils of glycoproteins including fibrillin, which assists in the formation and deposition of elastin.
Clinical Note: Mutations in the fibrillin gene are associated with Marfan’s syndrome (a connective tissue disorder).
Glycoproteins in ECM
Fibronectin: A key glycoprotein approximately 200 kDa in size; often exists as dimers formed from two different polypeptides that can bind and interact with ECM components and cells.
Structure of Fibronectin:
Contains binding domains for collagen, integrins, and heparin.
Functionality:
Fibronectin can undergo conformational changes upon stretching, thereby exposing hidden binding sites that facilitate the formation of fibronectin filaments.
Basal Lamina Structure
Definition: Basal laminae are specialized types of ECM found at the interface of epithelial cells and underlying connective tissue.
Typical Components:
Laminin, type IV collagen, nidogen, and proteoglycan perlecan.
Structure:
Comprised of polypeptide chains bound by disulfide bonds; 45 different laminin isoforms exist.
Diagram: Model for the structure showing ECM assembly as a cell-mediated process.
Objective 2: Cell-Matrix Junctions
Integrin Molecules:
Comprised of transmembrane heterodimers linking ECM to the actin cytoskeleton in cells.
Kindlin: A regulatory protein that modulates the activity of integrins and links them to the cytoskeleton.
Hemidesmosomes:
Function like spot welds, anchoring epithelial cells to the basal lamina through integrin connections to keratin filaments.
Integrin Types and Their Ligands:
Table 19-3 outlines various integrins, their ligands, tissue distribution, and implications of subunit mutations resulting in significant health issues, such as severe skin blistering or muscular dystrophy.
Signaling and Activation of Integrins
Conformational Changes: Integrins undergo changes from folded to extended states upon ligand binding, facilitating signaling pathways critical for cell behavior.
Talin's Role: Acts as a tension-sensor protein that can strengthen integrin linkages to the actin cytoskeleton, enhancing the stability of cell-matrix interactions.
Focal Adhesion Kinase (FAK): Recruited to focal adhesions, triggering intracellular signaling that can regulate cell division, growth, and survival in response to the cellular environment.
Review and Assignments
Homework Tasks:
Attempt the study guide questions provided.
Complete Problem Book exercises: Definitions (19-40 to 19-47), True/False (19-48 to 19-53 and 19-68 to 19-70), Thought problems (19-54 to 19-60 and 19-71).
Reading Material:
Chapter 19, Pages 1057-1081 for today's lecture.
Preparation for Next Lecture:
Read Chapter 20, Pages 1091-1114.
Watch Lecture 26 – Parts 1 & 2.