Learning Objectives

• Define and characterize the extracellular matrix (ECM).

• Delineate the roles of different ECM components.

• Identify the roles of Integrins in mammalian cells.

• Differentiate between models for cellular adhesion.

• Identify and differentiate between classes of molecules that mediate cell-cell interactions.

The Extracellular Matrix

• Extra: Means "outside" or "beyond."

• Matrix: Refers to a foundational structure or substance that other elements form from or develop within.

Major Components of the ECM

• Proteoglycans: Large molecules that play critical roles in ECM structure.

• Fibers: Provide mechanical strength.

• Organizers: Help to arrange matrix components.

• Examples: Laminin, Perlecan, Type IV Collagen, Fibronectin, Fibrillar collagens (e.g., types I, II), Nidogen/entactin.

Functions of the ECM

1. Anchoring and surrounding cells to maintain solid-tissue three-dimensional architecture and define tissue boundaries

   2. Determining the biomechanical properties (stiffness/elasticity, porosity, shape) of the extracellular environment

   3. Controlling cellular polarity, survival, proliferation, differentiation, and fate (e.g., asymmetric division of stem cells; see Chapter 22), and thus embryonic and neonatal development and adult function and responses to the environment and to disease

   4. Inhibiting or facilitating cell migration (e.g., serving as either a barrier to movement or, conversely, as a “track” along which cells — or portions of cells — can move)

   5. Binding to and acting as a reservoir of growth factors; in some cases, the ECM (a) helps generate an extracellular concentration gradient of the growth factor, (b) serves as a co-receptor for the growth factor, or (c) aids in proper binding of the growth factor to its receptor (ECM component and growth factor jointly serve as a receptor’s combined ligand)

   6. Activating cell surface signaling receptors

Tissue Variations of ECM

• The ECM’s composition varies significantly across different tissue types.

• Ex: Connective tissue vs tightly packed epithelial cells and their associated fibroblasts.

Plant Comparative Matrix

• Cell walls constitute the supportive matrix in plant tissues. Cell walls = their supportive matrix

• Cellulose and Pectin are primary components.

• Arabidopsis thaliana serves as a model organism in these studies.

Cell Adhesions

• Connections between cells are vital for multicellularity.

• Different adhesions serve distinctive roles, making multicellularity feasible.

Animal Tissues and Their Functions

• Epithelial Tissue: Covers and protects; includes squamous, glandular types.

• Muscular Tissue: Involved in movement, includes striated (skeletal, cardiac) and non-striated types.

• Connective Tissue: Provides support; includes blood, lymph, adipose, cartilage, and bone.

• Nervous Tissue: Responsible for communication and coordination.

Epithelial Cell Model

Cellular Structures

• Models display various cell adhesion molecules (CAMs), including tight junctions, adherens junctions, desmosomes.

• Features of cell-cell adhesion mechanics visualized through cellular interactions.

Adhesion Receptors

• Cell surface molecules, known as adhesion receptors, play a critical role in cell communication. 2 types::

  • Cell-Cell Adhesion

  • Cell-Matrix Adhesion

• CAM is important for communication. No communication is bad for the system.

• Major CAM families: Cadherins, Immunoglobulin (Ig) superfamily, Integrins, and surgar binding proteins called Lectins

Adherence Molecules

• Homophilic interactions: CAD molecules interact between the same cell types.

• Heterophilic interactions: CAD molecules interact with different cell types.

• Key CAM examples include E-Cadherin and Selectins.

Cis/Trans Interactions

• Cadherin molecules engage in both cis (within the same cell) and trans (adjacent cells) interactions, promoting cellular cohesion. The ability to mic and match them makes them a versatile family of proteins.

Page 14: Information Relay

• Cell adhesion molecules connect to signaling pathways, affecting cell behavior based on adhesion status.

Page 15: Engagement Changes

• Adhesion molecules can transmit mechanical signals through conformational changes, recruiting other proteins for reinforcement.

• Adhesion molecules can be mechanotransducing. Fibronectin stretching in the ECM form cells nearby can cue recruitment of further proteins for reinforcement by revealing cryptic binding sites

Cell Junctions

Epithelial Cells

• Function: Line, protect, absorb, secrete, cushion.

• Classified as simple (one cell layer) or stratified based (2+ layers) on cell layers.

Epithelial Cell Interactions

Cadherin Zippers

• Adherens junctions utilize cadherin interactions to form zipper-like structures, enhancing cell adhesion. Adherens junctions connect the lateral membranes of adjacent epithelial cells near the apical surface, below tight junctions

• Cadherin molecules interact with each other in the same cell (cis) or with adjacent cells (trans) to create a zipper

• Individual interactions = weak, en masse = strong

Desmosomes

• Act as strong adhesion sites that connect cells through cadherin proteins, adding strength through intermediate filaments.

• Important in diseases affecting cell-adhesion integrity. Characterized by defects in adhesion: cell - cell and/or cell-substrate

Page 22: Hemidesmosomes

• Function to anchor epithelial cells to the basal lamina, dancing analogously to traditional desmosomes.

• Kertain filament = intermediate filaments; spot welding to the basal lamina

• 

Integrins Activated by Binding Target

• integrin are a large family of alpha/beta heterodimeric cell surface proteins that play a crucial role in cell adhesion and signaling, facilitating the connection between the extracellular matrix and the cytoskeleton.

Dynamics of Integrin Function

• Integrins modulate both cell-cell/matrix interactions and adapt conformation to engage with varying targets.

• they exhibit differing conformational states that alter affinity for targets

• a6b4 is the main laminin binding one in epithelium

Tight Junctions Overview

Characteristics

• Seal body cavities, restrict the diffusion of membrane components, important in maintaining barrier integrity in epithelial tissues. It keeps the fluids separated between the epithelial cell layer.

• they form ring structures around the top of the cells. Rings are connected to adjacent cells rings.

Key Proteins

• Many integral membrane proteins are involved in tight junctions.

• Occludin, Claudin, and Tricellulin contribute significantly to forming tight junctions across epithelial cells.

  • Occludin and Claudin are highly studied

  • Tricellulin appears where three cells tight junctions meet

  • Junction Adhesion Molecules (JAM) so involved.

• 

Tight Junction Interaction

Adapter Proteins

• Adapter proteins interact with these proteins in tight junctions including Zona occludens proteins mediate transcellular transport, influencing solute movement between cells.

Gap Junctions

• Large complexes found in junctions amidst the gaps

• Facilitate cell communication through connexon channels that allow small molecules and ions to pass between cells.

• 6 protein TM connexon units form hemichannels that connect to adjacent cells.

Tunneling Nanotubes

• Connect adjacent cells and facilitate the transfer of organelles and smaller molecules, enhancing intercellular communication.

Basal Lamina Structure

• Layers of the basal lamina consist mainly of Type IV collagen, laminin, and nidogen, serving as a foundation for epithelial cells.

• Mat like structure; sheets of epithelia sit on basal lamina

Laminins

• Laminins are multi-adhesive proteins critical for the structure of the basal lamina and serve as binding sites for integrins.

• has a cross like trimer (a, B, y)

• they self assemble into large structures using their globular domains.

• C terminal domains allow for binding by cell receptors, including some integrins.

  

Collagen Structure

• Collagen forms a triple-helix structure formed from left handed helical proteins and is the most abundant protein in animals, playing a vital role in tissue strength.

• characteristic glycine-x-y repeats. the bundles form right hand helices.

Connective Tissue

Bone Structure

• Matrix constitutes the majority of bone with collagen fibrils and calcium phosphate contributing to its structure and strength.

• cells are dark spots

• bands contain collagen fibrils

• calcium phosphate also present

Collagen Bundles

• Formation of collagen fibers (superstructure) occurs via fibroblasts and osteoblasts, crucial for maintaining connective tissue integrity. Built by:

  • fibroblasts - skin

  • osteoblasts -bone

  • exocytosis

• Cross linked triple helix

Collagen Synthesis

• Collagen synthesis involves procollagen production (IC), secretory vesicle formed, and self-assembly into functional fibers.