Week 6: Cell Movement, Extracellular Structures and Cell Communication

Learning Resources

  • Textbooks:

    • Biological Chemistry - Chapters 5 & 6

    • Publisher: Pearson

    • Institution: Glasgow Caledonian University

  • Compiled by: The Biological Chemistry Module Team at Glasgow Caledonian University

Learning Objectives

  • Understand how cells move by:

    • Crawling (migrating)

    • Flagella and cilia

  • Consider the extracellular matrix (ECM) and its support for cells

  • Understand the importance of cellular junctions and communication

Key Concepts in Cell Movement

  • Cell Movement Methods:

    1. Cell cytoskeleton:

    • Present in mammalian cells (e.g., skin cells, lymphocytes, macrophages)

    1. Flagella and cilia:

    • Present in bacteria and mammalian cells respectively

  • Dependence on Cytoskeletal Structures:

    • All cell motion depends on the movement of:

→ Actin filaments

→ Microtubules

→ Both types in some cells

  • Cell Crawling:

    • Some cells migrate using actin microfilaments

    • Cell migration is an active process

Cell Migration Process

  1. Protrusion of Leading Edge:

  • Actin network pushes forward in the direction of motion

  1. Adhesion at Leading Edge:

  • Actin cortex is under tension, resulting in adherence to the substrate

Deadhesion at Trailing Edge:

  • Release of adhesion allows movement

  1. Movement of Cell Body:

  • Contraction pulls the rest of the cell forward

Importance of Cell Migration

  • Cancer

  • Inflammation

  • White blood cell movement

  • Wound healing (keratinocytes, fibroblasts, angiogenesis/endothelial cells → blood vessel cells)

  • Directional Cell Movement

    • Chemotaxis:

      • Cells move towards chemical signals (cytokines, antigens, bacterial cell wall proteins, signalling molecules → e.g Protein Kinase A)

      • Critical for early development e.g movement of sperm in fertilisation

      • Involved in the migration of neurons during development and lymphocyte in blood vessels

      • Movement can be disturbed in conditions like cancer

Importance of Cell Migration

  • Key roles in various physiological processes:

    • Cancer progression

    • Inflammation response

    • White blood cell movement

    • Wound healing (involves keratinocytes, fibroblasts, and vascular cells)

Cytoskeletal Filaments

  • Actin and Microtubules:

    • Actin: Predominantly at cell front, responsible for protrusion and adhesion.

    • Microtubules: Stabilise cellular structures during migration, formed behind the leading edge to assist in cell body movement

  • Mechanism of Action:

    • Actin filaments polymerize and contract via myosin motors, facilitating movement forward

Structure of Actin Filaments

  • Monomer (G-actin) vs. Filament (F-actin):

    • G-actin: Individual globular protein unit

    • F-actin: Polymerised strands which form the cytoskeletal structure

  • Inhibitory Factors for Actin Formation:

    • Ratio of free actin to profilin-bound actin

    • Presence of actin-capping proteins

Integrins and Extracellular Matrix Interaction

  • Integrins:

    • Connect ECM to cell cytoskeleton

    • Facilitate migration through signaling pathways

    • Influence cell behaviour and adhesion by interacting with actin stress fibers

  • Structure of Integrin Complexes:

    • Composed of multiple proteins and signaling pathways, including RTKs (Receptor Tyrosine Kinases) and pathways influencing proliferation, differentiation, and survival.

Microtubule-Based Motility

  • Microtubules are assembled by α/β dimers.

  • Form a strand, growing from the '+' end.

  • Connected to the centrosome.

  • Form behind the actin leading edge.

  • Ends of the microtubules push forward and pull in the direction of movement.

Movement by Flagella and Cilia

  • Structures:

    • Flagella: Projections of cells with a rotary motion and can be sequenced oriented

    • Cilia: Multiple shorter projections, involved in transport and movement (found in structures like intestines and lungs)

  • Motor Proteins:

    • Dynein: Drives the movement of flagella and cilia through a 9 + 2 arrangement of microtubules, allowing for coordinated motion

Primary Cilia Function

  • All cells develop a primary cilium during growth arrest, acting as a signaling hub in various biological processes

  • Key roles in:

    • Mechanosensitive signalling

    • Coordination of other cellular signals in tissue homeostasis

Components of the Extracellular Matrix (ECM)

  • Structure:

    • Composed of glycoproteins like collagen, fibronectin, elastin, proteoglycans

    • Collagen: Major component; provides structural support

    • Proteoglycans: Form the protective layer around cells

  • Macromolecule Types:

    • Collagens, elastin, proteoglycans, adhesive glycoproteins, hyaluronan (HA)

  • Collagen:

    • Essential for the structure of bones and tissues (40% of total amount of protein in the human body), with mutations leading to various diseases

→ Skin disease - lupus and Rheumatoid arthritis

→ Vascular disease - temporal arterits

Elastin

  • Protein in the ECM of connective tissue.

  • Allows tissues to resume their shape after stretching or contracting.

  • Helps skin to return to its original position when deformed.

  • Load-bearing tissue (used where mechanical energy must be stored).

Fibronectin

  • High-MR (~440kDa) glycoprotein.

  • Binds to integrins.

  • Binds collagen, fibrin, and heparin sulfate proteoglycans.

  • Exists as a protein dimer - two nearly identical monomers (A and B) linked by disulphide bonds).

Fibrin

  • Forms the clot that forms over wounds to seal them.

  • Cross-linked fibrin is part of the ECM.

  • Fibrin deposition commonly observed in angiogenesis associated with wound healing and tumor growth.

Proteoglycans and Glycosaminoglycans (GAGS)

  • Proteoglycans are a large family of proteins associated with the ECM.

  • Many cells synthesise proteoglycans and secrete them into the ECM.

  • Major constituents of connective tissues, basement membrane, and cartilage.

  • GAGs are long polysaccharides (repeating disaccharide unit covalently bind to proteoglycans).

Functions of ECM

  • Provides structural support

  • Influences cell behaviour through signalling

  • Cell adhesion and differentiation

  • Composition is highly variable, reflecting the needs of different tissues and developmental stages

Cell-Cell Interactions and Junctions

  • Tissue Organization:

    • Cells of the same type interact and function as a unit to form tissues (e.g., muscle and nervous tissue)

  1. Anchoring Junctions: Mechanically attach cells and their cytoskeleton to adjacent cells and the ECM.

  • Actin filament attachment sites:

    • Cell-cell junctions: adherens junctions

    • Cell-matrix junctions: focal adhesions

  • Intermediate filament attachment sites:

    • Cell-cell junctions: desmosomes

    • Cell-matrix junctions: hemidesmosomes

  1. Occluding Junctions: Seal cells together, preventing leakage of molecules (e.g., tight junctions).

  2. Communicating Junctions: Cell-cell junctions (gap junctions).

Communicating Junctions

  • Intercellular communication junctions:

    • Cell-cell junctions: connexins channels (gap junctions)

    • Extracellular signaling junctions: pannexin channels

Gap Junctions

  • Plaque-like structure.

  • Formed from connexins (membrane proteins).

  • Allow intercellular exchange of water, inorganic ions, and small biomolecules (below 1 kDa).

  • Integrate electrical and metabolic activities of cells.

→ e.g., heart muscle and synchronous beating

Formation of Gap Junctions

Connexins oligomerize to form connexons, which then dock to form gap junctions.

Connexin Structure and Interactions

  • At least 20 subtypes, named based on molecular weight.

  • Carboxyl tail of Cx43 subject to post-translational modification (e.g., phosphorylation).

  • Changes in phosphorylation status modify protein function.

Roles of Gap Junction Intercellular Communication

  • Heart: synchronization of heartbeat

  • Hearing: recycling of K+K+ ions, maintaining endocochlear potential

  • Skin: role in cell proliferation, differentiation, and metabolism

  • Vascular cells: contraction of smooth muscle cells, signal transduction along the endothelium

  • Nerves: action potential

Review Questions

  • What are the two main structures that support eukaryotic cell movement?

  • How does actin promote cellular movement?

  • How are flagella formed?

  • What are the main functions of the ECM?

  • Name the components of the ECM.