INTEGRATION OF CELLS INTO

TISSUESDr Mahmood S Choudhery, PhD

Assistant Professor

Advance Center of Research in Biomedical Sciences

Incharge Tissue Engineering Laboratory, Mayo Hospital Lahore, Pakistan

King Edward Medical University, Lahore, Pakistan

Learning objective

How cells attach to neighboring cells How cells communicate with other

cells and extracellular matrix (ECM) Types of different junctions Role of ECM in cell signaling

Levels of Organization in Living Things

Why cells integrate to

form tissues?

They need to perform specific functions more effectively

Permits the organism as a whole to move,

metabolize, reproduce, and carry out other essential

activities.

Integration of Cells into TissuesInvolves 2 processes

1. Cell Recognition

2. Cell Adhesion

Cell Adhesion……………

1.Cell-cell adhesion

2. Cell-matrix adhesion

Adhesion Receptors

Cells can adhere to each other by two ways

Cell Adhesion Molecules (CAMs)

Cell Adhesion Molecules (CAMs)………..

1. Are proteins (glycoproteins) 2. Involved in binding with other cells or with ECM3. Typically transmembrane proteins4. Cluster to form specialized cell junctions

Cell Adhesion Molecules……….. 4 Types

CadherinsImmunoglobulinsIntegrinsSelectins

TYPES OF INTERACTIONS

Between adhesion molecules Homophilic interactions Heterophilic interactions

Between cells Homotypic interactions Heterotypic interactions

What are Cis and Trans interactions?

SPECIALIZED CELL JUNCTIONS

Between cellsTight junctionsAdhesive/ Anchoring junctionsGap junctions

Between cells and matrixHemidesmosomesFocal Junctions

1. Cell Junctions- types based on localization

2. Cell junctions - types based on function

Adhering junctions:1. Tight junctions

2. Adhesive/ Anchoring junctions

3. Hemidesmosomes

4. Focal Junctions Communicating junctions:

1. Gap junctions

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1. Tight Junctions

Only found in epithelial cells Composed of 3 transmembrane protein families Prevent substances from moving through intercellular

spaces

2 typesa) Desmosomes

b) Adherens Junctions

2. Adhesive/ Anchoring junctions

Hold cells tightly together Connect a cell’s cytoskeleton to another cell

a) DESMOSOMES HOLD CELLS TOGETHER

1. Form links between cells2. Connect intermediate filaments of adjacent cells3. Composed of cadherins

Under the cell membrane, contractile fibers of microfilaments connect to cell membrane proteins called cadherins

b) Adherens Junctions

E- cadherin mediated adherens junctions Homophilic pairing of E- cadherins Adapter proteins (plakoglobin and α and βcatenins)

link cadherins to the belt of actin filaments.

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3. GAP JUNCTIONS

Gap junctions allow cells to exchange electrical and/or chemical signals

Composed of proteins that form channels that allow small molecules to pass.

Subunits of these channels are connexins that are assembled together to make connexons. The connexons from 2 cells join together to make a gap junction.

Gap Junctions

This channel is big enough to allow small molecules such as inorganic ions, and other small water soluble molecules (smaller than 1000kDa) to pass between the cells. However the channel is too small for proteins, nucleic acids or sugars to pass through.

Cell Communication Structures

Gap Junctions

desmosomedesmosomeGap Junctions:pairs of channelsconnect insides ofadjacent cells

Gap Junctions:pairs of channelsconnect insides ofadjacent cells

LiverLiver Plasma membrane(edge view)Plasma membrane(edge view)

Liver cellsLiver cells

Plasmodesmata

Plasmodesmataconnect insidesof adjacent cells

Plasma membrane(edge view)

Root cells

Cell wall(edge view)

Middle lamella(edge view)

RootRoot

Animals Plants

4. Hemidesmosome Connections between cell and ECM Composed of Integrins

What is ExtraCellular Matric (ECM)?

•Secreted by surrounding cells

EXTRACELLULAR MATRIX

1. Basal lamina

2. Interstitial Matrix

Two types of Extracellular Matrix

ECM COMPONENTS

1. Proteoglycans 2. Structural Proteins (Collagens and

Elastins) 3. Adhesive Glycoproteins (Fibronectins

and Laminins)

1. Proteoglycans: (Protein-polysaccharide complexes)

ECM components…………….

Composed of a core protein and GAGsHave net negative chargeTrap and store growth factors

2. Structural Glycoproteins (Collagens and Elastins)

ECM components…………….

3. Adhesive Glycoproteins (Fibronectins and Laminins)

Collagens are the main proteins of ECMElastin give elasticity to tissues

Fibronectin connect cells with collagen fibers in the ECM and integrin receptors on cell membraneLaminin found in the basal lamina

Role of Extracellular Matrix in Cell Signaling

Provides space where different ligands and growth factors are released

Act as a reservoir for various growth factors

Different proteins of ECM act as ligand for cell receptors

How Extracellular Matrix Components Mediate Cell Signaling?

Integrins are transmembrane receptors for extracellular matrix (ECM) proteins such as collagens, fibronectin, laminins and vitronectin.

The Extracellular Matrix Participates in Signaling

lntegrin adhesion receptor mediated signaling pathways that control diverse cell functions.

Recommended Books

• Molecular Cell Biology By Lodish 7th

• Molecular Biology of The Cell by Bruce Alberts