Integrating Cells into Tissues

Lecture 16: Integrating Cells into Tissues: Inner Ear Cochlea

Major Topics Covered in Lecture

  • Integrating Cells into Tissues

  • Overview of adhesion processes involving cell-cell and cell-extracellular matrix (ECM) interactions

Learning Objectives

  • Define the extracellular matrix (ECM)

    • General structure: Dynamic, complex meshwork of proteins and polysaccharides.

    • Function: Contributes to tissue structure and function.

  • Describe the function and structure of basement membranes (basal lamina)

    • Role in organizing cells into distinct tissues, acting as a barrier, and guiding cell migration.

  • Differentiate between ECM components

    • Collagen: Major structural component, forms fibers.

    • Glycosaminoglycans (GAGs): Polysaccharides that provide cushioning.

    • Proteoglycans: Glycoproteins linked to GAGs that regulate cellular interactions.

    • Glycoproteins: Proteins that facilitate cell adhesion and signal transduction.

  • Clarify steps in cell adhesion to non-cellular surfaces

    • Involves receptor-ligand interactions between cells and ECM components.

  • Describe membrane proteins involved in adhesion

    • Cell adhesion molecules (CAMs) and adhesion receptors.

  • Describe structures and functions of cell junctions

    • Types: Tight junctions, gap junctions, adherens junctions, desmosomes, hemidesmosomes.

Important General Concepts on Cell-Cell and Cell–ECM Adhesion

  • Critical Functions:

    • Assembly of cells into tissues.

    • Controlling cell shape and function.

    • Determining developmental fate of cells and tissues.

  • Cell-Adhesion Molecules (CAMs):

    • Mediate direct cell-cell adhesions (both homotypic and heterotypic).

    • Adhesion receptors facilitate cell-matrix interactions.

  • Dynamics of ECM:

    • It facilitates structural support and signal transmission in tissues.

Overview of Major Cell-Cell and Cell-Matrix Adhesive Interactions

  • Types of Adhesive Interactions:

    • Cell-Cell Adhesions: Connect adjacent cells.

    • Cell-Matrix Adhesions: Connect cells to the ECM

Components of Adhesive Interactions

  • Cell Adhesion Molecules (CAMs): Integral membrane proteins facilitating interactions.

  • Tight Junctions: Block solutes, regulate paracellular transport, and maintain distinct cell polarity. - separate apical and basal cells, prevent diffusion of lipids and proteins, thus ensuring that cellular environments maintain their specialized functions.

    • Paracellular transport- permeability to ions, small molecules and water varies enormously among different epithelial tissues

    • Transcellular transport of molecules across epithelia- cellular uptake on one side and release on the opposite side.

  • Gap Junctions: Allow exchange of small molecules and ions between adjacent cells. -small ions and small molecules to pass through adjacent cells

  • Adherens Junctions: Connect neighboring cells through actin filaments.

  • Desmosomes: Link intermediate filaments between cells for mechanical stability. - small, localized attachments within the cell

  • Hemidesmosomes: Connect cells to the ECM through integrin adhesion receptors.

  • Inside out signaling- signal coming from the cell that will modify the extracellular environment

  • Outside in signaling- Binding of extracellular ligands to integrins changes their conformation, impacting their interactions with signaling proteins, thus influencing cell functions.


Additional Notes on Epithelial Tissue Structure

  • Intestinal Epithelial Tissue:

    • Contains microvilli on the apical surface for nutrient absorption.

    • Examples of junction types: Tight junctions near the microvilli for sealing.

Major Families of Cell-Adhesion Molecules (CAMs) and Adhesion Receptors

  1. Cadherins: (Homophilic)

    • Ca2+-dependent homophilic interactions allowing adherence between similar cells.

    • Examples include E-cadherin, which associates in epithelial tissues.

  2. IgCAMs (Immunoglobulin-like CAMs): Ig superfamily CAMs (homophilic)

    • Form both homophilic and heterophilic interactions, contributing to various cellular functions. form heterophilic linkages

  3. Integrins: (Heterophilic)

    • Heterodimeric proteins (α and β chains) binding to ECM proteins for cell-matrix adhesion.

    • Bind to very large matrix proteins like fibronectin.

  4. Selectins: (heterophilic)

    • Bind specifically to carbohydrate structures on glycoproteins/glycolipids, crucial for leukocyte interaction with endothelium. Bind to certain sugars

Mechanisms of Cell-Cell Adhesion Formation-examples-cadherins

  • Cis Interactions: Lateral clustering of CAMs within the same cell membrane.

  • Trans Interactions: Intercellular interactions that form strong adhesive connections, akin to velcro. Stronger that cis interactions

Both cis and trans interactions are mutually reinforcing, providing structural integrity.

Functions of the ECM (Table 20-2)

  1. Anchoring cells to maintain tissue architecture and boundaries.

  2. Defining biomechanical properties (stiffness, elasticity).

  3. Controlling cellular behaviors like polarity, survival, proliferation, and differentiation.

  4. Influencing cell migration and acting as barriers or tracks.

  5. Reservoir for growth factors and aiding their binding.

  6. Activating cell surface signaling receptors.

Density variation of cells and ECM in different tissues-

  • Dense Connective Tissue: High ECM density with sparse fibroblasts. pink rows relatively sparse fibroblasts

  • Sparse Connective Tissue: Closely packed epithelial cells with minimal ECM between them. quilt like pattern

Key Components of the Extracellular Matrix (ECM)

ECM Proteins

  • Collagens:

    • Most prevalent ECM proteins, contributing to structural framework.

  • Proteoglycans:

    • Unique glycoproteins providing hydration and cushioning.

  • Fibronectin and Laminin:

    • Multi-adhesive proteins interconnecting various matrix components and playing roles in cell adhesion.

Functions of the ECM

  • Tissue Architecture:

    • Supports the three-dimensional structure and cellular organization.

  • Biomechanical Properties:

    • Influences tissue stiffness, elasticity, and cellular behavior.

  • Cellular Functions:

    • Regulates cell growth, migration, and differentiation through binding interactions.

  • Activating cell surface signaling receptors

Signaling Pathways Influenced by Integrins

  • Integrins influence:

    • Cell survival

    • Gene transcription

    • Cytoskeletal organization

    • Cell motility and proliferation through inside-out and outside-in signaling mechanisms.

Inside-Out Signaling

  • Adapter proteins modify integrins to enhance their binding capacity for ECM components.

Outside-In Signaling

  • Binding of extracellular ligands to integrins changes their conformation, impacting their interactions with signaling proteins, thus influencing cell functions.

Mechanotransduction in Cells- outside in signaling

  • Mechanotransduction: Interconversion between mechanical stimuli and biochemical responses.

  • Fibronectin Domains: Under mechanical stress, fibronectin can unfold, revealing binding sites essential for ECM assembly.

  • Talin Dynamics: Talin unfolds under mechanical tension, promoting vinculin binding, which strengthens integrin-mediated adhesion.

  • Sensing stretch or deformation of the ECM

  • Key in this is things such as the ability of cells to sense and respond to changes in the extracellular matrix (ECM), allowing them to adapt their behavior and maintain tissue integrity.

  • Crucial for functions are the ability to hear, touch, and muscle adaptation.

Structures of the Extracellular Matrix: The Basal Lamina

  • Basal Lamina: A crucial component connecting epithelial and other organized cell groups to connective tissues.

  • Components:

    • Contains laminin, type IV collagen, perlecan, and nidogen.

Functions of Basal Lamina

  • Organizes cells into tissues.

  • Protects cells and guides their migration during developmental processes.

  • foundation for assembly of cells into most tissues

  • part of the ECM but a specialized part- thin sheetof proteins and carbohydrates known as the basement membrane, which provides structural support and regulates molecular exchanges between cells and their environments.

  • Laminin- can interact with collagens (80% of the ECM), integrins, and even some laminin via. laminins make-calcium dependent interactions. Multi adhesive protein.

Collagen Structure and Types

  • Collagen Structure:

    • Composed of varying polypeptide chains organized into triple helices, providing strength and flexibility to tissues.

    • triple helix- contains repeating sets of Gly- Pro- X amino acids. Collagens can make things such as muscles for example. can interact laterally or even head to tail

Types of Collagen

  • Fibrillar Collagens (e.g., Type I, II, III): Provide tensile strength.

  • Fibril-Associated Collagens (e.g., Type VI, IX): Support fibril architecture.

  • Sheet-Forming Collagens (e.g., Type IV): Integral to basal lamina structure.

  • Transmembrane Collagens (e.g., Type XVII): Present in specific cellular localizations.

    • Pre-procollagen-immature collagen

    • procollagen- precursor is synthesized in the endoplasmic reticulum, where it undergoes post-translational modifications before being secreted into the extracellular matrix.

    • Procollagen proteinases- enzymes that process procollagen into mature collagen, playing a crucial role in the extracellular matrix formation.

    • Matrix proteinases- a way for cells to modify their ECM environment

Essential Concepts on Adhesive Interactions

  • Cell Surface Specialties: Integrins facilitate interactions with ECM and support adhesion.

  • Heterodimeric Nature of Integrins: Contributes to specificity in binding to distinct ECM proteins.

  • Dystroglycan and Dystrophin Complex: Provides structural linkage between the cytoskeleton and ECM in muscle cells.

Summary of Important Points

  • Adhesion Mechanisms: Strong, facilitated by adherens junctions, desmosomes, tight junctions, and gap junctions.

  • Cell Communication: Ensured through specialized structures like gap junctions, allowing direct cytoplasmic connections.

  • Functional Coordination: Adhesion molecules play a pivotal role in coordinating cellular responses to environmental cues, facilitating tissue integrity and function.

  • Integrins facilitate connections between cells and ECM; influence overall cellular behavior.

  • Anchoring junctions

    • Adherenes-cell to cell—cadherins- shape, tension, signaling, force transmission

    • Desmosomes-cell to cell-desmosomal cadherins- intermediate fillaments- strength, durability, signaling

    • Hemidesmosomes- cell-matrix- integrin- intermediate filaments- shape, rigidity, signaling

    • focal adhesions - cell-matrix - integrin - actin filaments - shape, signaling, force transmission, cell signaling

  • Tight junctions-cell to cell-occludin,claudin, JAM’s- actin filaments-controlling solute flow, signaling

  • Gap junctions- cell to cell- connexin, via adapters to other junctions- communication small-molecule transport between cells

    • Connexins are organized to 6 individual connexon proteins

  • Cadherins- cadherin reactions with other cadherins is calcium dependent

    • E(epithelial)- mediate adhesive connections in cultured MDCK epithelial cells

    • N(neural)

    • P(Placental)