Cell adhesion lecture 2024

Cytoskeleton

Definition: The cytoskeleton is a complex network of protein fibers and tubules that provides critical structural support, shapes the cell, and facilitates movement and intracellular transport, playing a vital role in maintaining cellular integrity, organization, and mobility.

Types of Filaments:

  • Microfilaments: Diameter of approximately 5 nm, primarily composed of actin, they are involved in various cellular functions including maintenance of cell shape, muscle contraction, and cell motility through processes like amoeboid movement and cytoplasmic streaming.

  • Intermediate Filaments: Roughly 10 nm in diameter, these are made up of a variety of proteins (such as keratin, vimentin, and neurofilaments) and provide mechanical strength to the cell, stabilizing its structure and resisting tension.

  • Microtubules: With a diameter of about 25 nm, these are hollow tubes made of alpha and beta tubulin proteins. They play a crucial role in maintaining cell shape, enabling intracellular vesicle transport, forming the mitotic spindle during cell division, and facilitating flagellar and ciliary movement in motile cells.

Roles:

  • Provides mechanical support to the cell and maintains its shape.

  • Facilitates cell division: Microtubules form the spindle apparatus that segregates chromosomes during mitosis.

  • Enables intra- and inter-cellular communication through the coordination of microfilament networks and signaling pathways.

Extracellular Matrix (ECM)

2.1 Example of Tissues

  • Connective Tissue: This diverse category includes adipose, fibrous, and cartilaginous tissues which provide structural support, bind other tissues, and play roles in storage and protection.

  • Muscle Tissue: Responsible for movement, can be voluntary (e.g., skeletal muscle) or involuntary (e.g., cardiac and smooth muscle), with specialized structures for contraction and signaling.

  • Nervous Tissue: Transmits electrical signals throughout the body, consisting of neurons that generate and propagate impulses and supporting cells (glia) that protect and nourish neurons.

  • Epithelial Tissue: Covers body surfaces and lines cavities, providing protection, absorption, secretion, and sensation, reliant on junctional complexes for integrity and function.

2.2 Connective Tissue

Types:

  • Adipose Tissue: Primarily stores energy in the form of fat and provides thermal insulation.

  • Cartilaginous Tissue: Provides flexible support, reduces friction at joints, and aids in shock absorption.

  • Blood Connective Tissue: Serves crucial roles in transportation of nutrients, gases, and waste products, and is involved in immune responses (e.g., leukocytes).

  • Osseous Connective Tissue: A rigid connective tissue that forms bones, providing essential structural support, facilitating movement, and protecting vital organs.

2.3 Composition of ECM

Main Components:

  • Glycosaminoglycans (GAG): Long, unbranched polysaccharide chains, often negatively charged, that retain water and help to form a gel-like substance in the ECM, maintaining hydration and structural stability.

  • Fibrillary Proteins:

    • Collagen: The most abundant protein in the ECM, provides tensile strength to tissues, forming a scaffold that supports cell attachment and growth.

    • Elastin: Provides elasticity and resilience to tissues, allowing them to stretch and recoil.

    • Fibronectin: A glycoprotein that binds cells to the ECM and helps in cell migration during development and healing.

2.4 Pathologies Related to ECM Alterations

Alterations in ECM components can lead to various pathologies, such as schizophrenia characterized by altered proteoglycans in the matrix, and the involvement of fibronectin in cell adhesion can be critical in understanding cancer metastasis.

2.5 Fibrillary Proteins

  • Collagen: Important for structural integrity; forms fibrils, undergoes maturation post secretion, and varies in type (e.g., Type I, II, III) depending on tissue type.

  • Fibronectin: Plays a critical role in cell adhesion and migration by binding to integrins, facilitating communication between the ECM and cells.

Junctional Complexes in Epithelial Cells

3.1 Basis of Adhesion

Cells adhere to one another and the ECM through:

  • Ca2+-Dependent Proteins: Integrins and cadherins help in mediating strong cell-cell and cell-ECM interactions.

  • Non-Ca2+-Dependent Proteins: Proteins like N-CAM and syndecans facilitate cell signaling and communication without the requirement of calcium ions.

3.2 Tight Junctions

Structure:

  • Formed by transmembrane proteins, such as occludins and claudins, these junctions seal neighboring cells together to create a barrier.

Function:

  • Prevent diffusion of molecules and ions through intercellular spaces, maintaining cell polarity and regulating paracellular transport.

3.3 Anchoring Junctions

Types:

  • Adherens Junctions: Link to actin filaments and provide structural integrity to epithelial layers.

  • Desmosomes: Provide mechanical strength by linking to intermediate filaments, involved in resisting shearing forces.

  • Hemidesmosomes: Anchor the basal layer of epithelial cells to the ECM, important for tissue integrity in areas subject to friction.

3.4 Gap Junctions

  • Formed by connexons, allowing direct communication between adjacent cells. They permit the passage of ions, small metabolites, and other signaling molecules, thus coordinating cellular activities.

Loss of Adhesion

4.1 Mechanisms of Loss

Loss of adhesion can occur due to changes in cell signaling pathways, degradation by proteases, and disruptions in matrix composition, affecting tissue integrity and function.

4.2 Loss of Adhesion and Normal Differentiation

This process is vital in physiological contexts such as axon guidance in neural development and during wound healing where re-epithelialization is necessary.

4.3 Loss of Adhesion and Pathological Differentiation

The loss of cell adhesion can contribute to cancer metastasis, underscoring the importance of cell-ECM interactions in tumor progression and the need for targeted therapies that address these mechanisms.