Interactions Between Cells and Their Environment

Introduction Cells don’t exist alone. Cells interact with extracellular material to form defined tissues. These interactions are crucial to the formation of epithelial tissue and connective tissue, which are crucial for various cellular activities.

Introduction (Cont.) Cell migration, cell growth, cell differentiation, 3-D organization of tissues and organs that emerges during embryonic development.

Overview of cell organization into tissues Click to edit Master text styles Second level Third level Fourth level Fifth level

7.1 The Extracellular Space (1) The glycocalyx (cell coat) is formed from carbohydrate projections form the plasma membrane. Outer surface of the plasma membrane

7.1 The Extracellular Space (cont.) Gycocalyx Mediate cell-cell and cell-substratum interactions Provide mechanical protection to cells Barrier to particles moving toward plasma membrane Bind important regulatory factors

The Extracellular Space (cont.) The extracellular matrix (ECM) is an organized network of proteins and polysaccharides beyond the plasma membrane. “Glue” that holds cells together It often plays a regulatory role in determining shape and activities of the cell.

Organization of the ECM

The Extracellular Space (cont.) ECM (continued) The basement membrane (basal lamina) is a continuous sheet that underlies epithelial tissue and surrounds blood vessels. Helps maintain cells attached. Serves as substratum for cell migration. Forms a barrier to macromolecules.

The basement membrane

Extracellular matrix Gel-like “ground substance” Primarily made of polysaccharides Gylycosaminoglycans (GAGs) proteoglycans Fibrous proteins Collagen, laminin, elastin, fibronectin Structure and adhesive functions

The Extracellular Space (cont.) Collagens – fibrous glycoproteins found only in the ECM. Collagen is the most abundant protein in the human body. Provide high tensile strength. Each collagen is restricted to particular locations in the body. All collagens are a trimer of polypeptide chains (α chains) and 3 polypeptide chains are wound around each other.

The structure of collagen I

Major types of collagen Type I collagen The chief component of tendons, ligaments, and bones. Type II collagen Represents more than 50% of the protein in cartilage and is the major component of the vitreous body of the eye. It is also used to build the notochord of vertebrate embryos.

Type III collagen Type IV collagen Strengthens the walls of hollow structures like arteries, the intestine, and the uterus. Type IV collagen Forms the basal lamina of epithelia. (The basal lamina is often called the basement membrane.)A meshwork of Type IV collagens provides the filter for the blood capillaries and the glomeruli of the kidneys.

The Extracellular Space (cont.) Collagens (continued) Provide the insoluble framework that determines mechanical properties of the matrix. Abnormalities in collagen formation lead to serious disorders.

The Extracellular Space (cont.) Collagens type I, II, III are fibrillar collagens Assemble into rigid, cable-like fibrils (assembles like fibers) Example: tendon – collagens are parallel to tendons thus parallel to pulling actions

The Extracellular Space (cont.) Abnormalities in fibrillar collagens formation can lead to serious disorders Mutation in in genes encoding type I collagen can produce osteogenesis imperfecta Extremely fragile bones, thin skin, and weak tendons

The Extracellular Space (cont.) Mutation in genes encoding type II alter the properties of cartilage tissue causing dwarfism and skeletal deformities Mutations in other collagens genes that are related in collagen matrix structure can lead to Ehler-Danlos sydromes Hyperflexible joints and extensible skin

The Extracellular Space (cont.) Not all collagens form fibrils. Collagen type IV is non-fibrillar, and is restricted to the basement membrane.

The Extracellular Space (cont.) Mutations in type IV collagen genes causes Alport syndrome A kidney disease in which glomerular basement membrane is disrupted

The Extracellular Space (cont.) Proteoglycans – protein-polysaccharide complex, with a core protein attached to glycosaminoglycans (GAGs). GAGs Have a repeating disaccharide structure. Negatively charged

The Extracellular Space (cont.) Negatively charged GAGs attract lots of cations, which in turn attract water forming a porous, hydrated gel. Function: to be able to withstand compressional forces through hydration and swelling pressure (turgor) to the tissue

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Structure of a proteoglycan complex

Structure of a proteoglycan complex

The Extracellular Space (cont.) Forms complement to collagen molecule Together, they give cartilage and other extracellular matrices strength and resistance to deformation Example: ECM of bones Collagen + Proteoglycans + calcium sulfate ions = bones GAG chains of proteoglycans also act as binding sites for many growth factors

The Extracellular Space (cont.) Fibronectin (Fn) Helps cells attach to matrix Fn has binding sites for other components of the ECM. RGD Binding of Fn to the cell occurs via the RGD sequence – binds to integrins

Structure of fibronectin

The Extracellular Space (cont.) Fibronectin (FN) is involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. Fibronectin sometimes serves as a general cell adhesion molecule FN also can serve to organize cellular

The Extracellular Space (cont.) Laminins – extracellular glycoproteins consisting of three polypeptide chains linked by disulfide bonds. Help cell migration during development. Components of basement membranes.

The Extracellular Space (cont.) Dynamic Properties The ECM can be stretched during tension. ECM materials degraded by matrix metalloproteinases (MMPs). MMPs possibly involved in tissue remodeling, embryonic cell migration, wound healing , and formation of blood vessels. Excessive MMPs causes arthritis, hepatitis, atherosclerosis, tooth and gum disease and tumor progression

7.2 Interactions of Cells with Extracellular Materials Integrins – family of membrane proteins composed of heterodimers with α and ß subunits. Have a major role in integrating extracellular and intracellular environments. Another role is adhesion of cells to their substratum or other cells.

Model of integrin activation

Interactions of Cells with Extracellular Materials (cont.) Integrins (continued) Linkage between integrins and their ligands mediates adhesion between cells and their environment. Binding of proteins to integrins is facilitated by tripeptide RGD.

Interactions of Cells with Extracellular Materials (cont.) Integrins (continued) Cytoplasmic domains of integrins contain binding sites for a variety of cytoplasmic proteins. Integrins make the connection between the ECM and the cytoskeleton.

Blood clotting Injury conformational change in platelets’ integrin activation inc. fibrinogen affinity aggregation of platelets Synthetic RGD peptides -> inhibit blood clot formation

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Interactions of Cells with Extracellular Materials (cont.) Focal adhesions are found at the cell membrane where the cytoskeleton interacts with proteins of the extracellular matrix Focal adhesions – scattered, discrete sites for cell adhesion to their substratum in vitro. They may act as a type of sensory structure. Are also implicated in cell locomotion.

The clustering of integrins at these sites attracts a large complex of proteins and initiates intracellular regulatory processes, by which such events as cell migration and anchorage-dependent differentiation are controlled. Focal adhesion kinase (FAK) is a protein tyrosine kinase which is recruited at an early stage to focal adhesions and which mediates many of the downstream responses. 

Focal adhesions

Focal adhesions

Interactions of Cells with Extracellular Materials (cont.) Hemidesmosomes are cell-substratum adhesion sites that connect the extracellular matrix to the keratin cytoskeleton basal attachments of epithelial cells to the basement membrane in vivo.Contain a dense plaque with filaments consisting of keratin.Keratin filaments are linked to the ECM by membrane-spanning integrins.

Junction Cytoskeletal Anchor Transmembrane Linker Ties Cell To: Desmosomes Intermediate filaments Cadherin Other Cells Hemidesmosomes Intermediate Filaments Integrins EC Matrix Adherens junctions Actin Filaments Cadherin/Integrins Other Cells / the EC Matrix

 form rivet-like links between cytoskeleton and extracellular matrix components such as the basal lamina that underlie epithelia

Hemidesmosomes

7.3 Interaction of Cells with Other Cells Cells have surface- recognition sites that maintain organization

Interaction of Cells with Other Cells (cont.) Selectins – family of integral membrane glycoproteins that bind to sugars on the surface of cells.

Interaction of Cells with Other Cells (cont.) Selectins (continued) Contain a small cytoplasmic domain, a single membrane-spanning domain, and a large extracellular segment. Three types: E-selectin – on endothelial cells. P-selectin – on platelets and endothelial cells. L-selectin – on white blood cells.

Interaction of Cells with Other Cells (cont.) Immunoglobulin superfamily (IgSF) – most proteins are involved in immune functions. Most IgSF molecules mediate interaction of lymphocytes with cells required or immune response.

TIGHT JUNCTIONS located at the apical end of the junctional complex between adjacent epithelial cells sites where integral proteins of two adjacent membranes meet block the diffusion of solutes and water “fences”

claudin – major structural component expressed in TAL claudin – 1 prevents water loss blood-brain barrier prevents drugs from entering CNS

GAP JUNCTIONS sites for intercellular communication plasma membranes come very close, but no contact composed of connexin subunit: connexon allow molecules less than 1000 daltons relatively nonselective

channel closure is triggered by phosphorylation of connexin have a potential to integrate individual cells into functional unit allow cells to share metabolites

connexons differ in conductance, permeability, and regulation promote or prevent communication mutation resulting to disorder might cause defects tunneling nanotubules conducting cell surface proteins

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PLASMODESMATA cytoplasmic channels that pass through cell walls desmotubule sites of cell to cell communication capable of dilation

gives polyhedral shape “skeleton” source of signal cellulose CELL WALLS bacteria, fungi, plants gives polyhedral shape “skeleton” source of signal cellulose fibrous component of cell wall protiens and pectin provide matrix

cellulose matrix cellulose synthase organized into rod-like microfibrils provide rigidity resistance to tensile forces polymerized at cell surface matrix synthesized in the cytoplasm three types of macromolecules

hemicelluloses bind to the surfaces of cellulose microfibrils pectins holds water proteins expansins – cell growth elongation

CELL WALLS thin cell plate provide suporrt primary walls secondary walls lignin structural support in xylem, move water through the plant