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Chapter 7 of Cell biology of Karp
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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 togetherIt 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 matrixGel-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 collagenType 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
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 imperfectaExtremely 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).
GAGsHave 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
• Click to edit Master text styles– Second level– Third level
• Fourth level– Fifth level
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)
Multiple binding domains
Complex proteins that binds to multiple substrates
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 clottingInjury conformational
change in platelets’ integrin activation
inc. fibrinogen affinity aggregation of platelets
Synthetic RGD peptides
-> inhibit blood clot formation
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.
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 claudin – 16
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
PLASMODESMATA cytoplasmic channels that pass
through cell walls desmotubule sites of cell to cell communication capable of dilation
CELL WALLS
bacteria, fungi, plants gives polyhedral shape “skeleton” source of signal cellulose
fibrous component of cell wall protiens and pectin
provide matrix
cellulose 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