1. Interactions Between Cells and Their Environment

2. 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.

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

4. Overview of cell organization into tissues
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5. 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

6. 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

7. 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.

8. Organization of the ECM

9. 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.

10. The basement membrane

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

12. 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.

13. The structure of collagen I

14. 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.

15. 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.

16. 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.

17. 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

18. 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

19. 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

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

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

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

23. 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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25. Structure of a proteoglycan complex

26. Structure of a proteoglycan complex

27. 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

28. 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

29. Structure of fibronectin

30. 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

31. 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.

32. 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

33. 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.

34. Model of integrin activation

35. 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.

36. 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.

37. 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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42. 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.

43. 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. 

44. Focal adhesions

45. Focal adhesions

46. 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.

48. 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

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

50. Hemidesmosomes

51. 7.3 Interaction of Cells with Other Cells
Cells have surface- recognition sites that maintain organization

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

53. 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.

54. 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.

55. 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”

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

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

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

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

65. 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

66. 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

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

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