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FoundSci Unit 4 > Extracellular Matrix > Flashcards

Extracellular Matrix Flashcards

1
Q

Interstitial Space

A

The space between cells in a tissue.

Equivalent to extracellular space in cells

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2
Q

Tissue Fluid

A

Interstitial Fluid or Intercellular fluid

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3
Q

What is the function of tissue fluid?

A

Diffusion and exchange medium for water soluble substances

Hydrates ground substance in ECM

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4
Q

Extracellular Matrix

A

Fibers embedded in an amorphous gel called ground substance.

Fibers are long water insoluble structural proteins. Mainly collagen fibers and elastic fibers

Ground substance is structural polysaccharides (GAGs and proteoglycans), linker proteins, and enzymes

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5
Q

What are the 2 forms of extracellular matrix?

A

Interstitial matrix

Basement membrane

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6
Q

What are the functions of the extracellular matrix? (x7)

A
  1. Confers structural properties to tissues
  2. Forms a physical connection between ECM and cells
  3. Structural stability
  4. Signaling
  5. Diffusion and Exchange medium
  6. Facilitates (or limits) cell migration
  7. Modulates development and cell proliferation
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7
Q

What role does the extracellular matrix play in early development?

A

The amount of space between cells affects cell proliferation

Cells use their physical connections to ECM to orient themselves in 3D space - once orientated, they know which direction to divide

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8
Q

What properties of the ECM can be attributed to fibers?

A

Tensile Strength
Elasticity
Compressive Strength

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9
Q

What properties of the ECM can be attributed to hydrated ground substance?

A

Compressive strength
Metabolite exchange/diffusion
Anchor cell to ECM
Tissue volume

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10
Q

Describe the structural organization of each collagen fiber type

A

Collagen I: Fibrils assemble into fibers that often group into fiber bundles

Collagen II: Fibrils that loosely aggregate

Collagen III: Fibrils branch and loop back; crosslink to form a 3D network

Collagen IV: Collagen molecules form a crosslinked, woven sheet

Collagen VII: Collagen molecules aggregate to form anchoring fibrils

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11
Q

What are the functions of each collagen fiber type?

A

Collagen I: Resist tensile force

Collagen II: Resist compression

Collagen III: Structure and support; forms scaffold in organs and glands

Collagen IV: Support and filtration

Collagen VII: Sutures lamina densa to lamina fibroreticularis in basement membranes

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12
Q

What are the main locations of each collagen type?

A

Collagen I: Tendons, skin, bone, fibrocartilage, organ capsules, scars

Collagen II: Hyaline and elastic cartilage

Collagen III: Spleen, liver, lymph nodes, adipose tissue, bone marrow, epithelial basement membranes

Collagen IV: All basal and external laminae (including basement membranes)

Collagen VII: Epithelial basement membranes

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13
Q

How does each collagen type appear in LM?

A

Collagen I: Thick, acidophilic

Collagen II: Very thin, slightly acidophilic

Collagen III: Thin, PAS+ and argyrophilic (+ rxn in silver stains)

Collagen IV: IHC (main), PAS+, argyrophilic

Collagen VII: IHC

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14
Q

Collagen I Fibers

A

Flexible, semi-rigid support structures

Resist tensile (pulling) forces

Tissues described as fibrotic usually have lots of collagen I fibers.

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15
Q

Collagen Fibril

A

Group of associated cross-linked parallel rows of molecules

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16
Q

How do collagen molecules line up to form fibrils and why?

A

Collagen molecules align end to end in parallel rows and cross links between adjacent rows of collagen molecules

Confers tensile strength to collagen 1 fibril/fiber

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17
Q

Collagen Molecule

A

Triple helix formed by 3 alpha chains

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18
Q

How are fibrils organized within a fiber?

A

Fibrils are uniform in diameter and spacing

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19
Q

List the collagen components from smallest to largest

A

alpha chains
collagen molecules
collagen fibrils
collagen fibers
collagen fiber bundles

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20
Q

What is the most abundant ECM fiber in the body?

A

Collagen I

21
Q

What are the characteristics of collagen I fiber?

A

Long, thick, and do not branch

Straight or wavy

Bundles may be parallel or go in multiple angles or directions

22
Q

Explain collagen I fibers and scarring

A

Collagen I fibers are the main component of scar tissue

During wound repair, white blood cells remove severely damaged tissue and dead cells. Any empty space is then replaced with collagen I fibers, forming a scar

Fibrosis - pathological form of wound healing, excessive disposition of collagen I fibers. Fibrosis interferes with normal tissue function

23
Q

What are the functions of collagen II fibers?

A

Provide internal structural support to hyaline and elastic cartilage

Resist compressive forces

24
Q

Reticular fibers

A

Collagen III fibers

Support and suspend cells in solid tissues/organs

Forms a 3D internal scaffold/mesh that supports and suspends cells or cell clusters

Made of reticulin. Branch and reticulate in all 3 axes

25
Q

Reticulating

A

Looping back on itself

26
Q

How do reticular fibers stain?

A

Stain poorly in H&E and are PAS+.

Argyrophilic

Reticulin specific stain or IHC for reticulin

27
Q

How are collagen molecules synthesized and where do they assemble?

A

Intracellular protein synthesis and extracellular assembly

28
Q

What cells make most collagens?

A

Fibroblasts - make many collagen types in connective tissue in ECM

Osteoblasts - collagen I in bone ECM

Chrondroblasts - Collagen II in cartilage ECM

29
Q

What forms the alpha chains in collagen synthesizing cells?

A

Ribosomes at RER surface

30
Q

What happens after ribosomes at RER surface synthesize alpha chains?

A

Alpha chains have nonhelical propeptides on ends that keep the alpha chains water soluble. Nonhelical propeptides prevent premature assembly from occurring within the cell

Chaperonins in RER cisterns do initial hydroxylation and glycosylation and fold alpha chains into triple helix, forming procollagen molecules

31
Q

How do collagen fibers self-assemble extracellularly? What is this called?

A

Enzymes in ECM convert procollagen molecules to collagen molecules

Fibrillogenesis - collagen molecules self-align and self-assemble into collagen fibrils

Fibrillogenesis happens outside cell

32
Q

Why does fibrillogenesis occur outside the cell?

A

Large, self-assembling water insoluble molecules would be huge problem inside the cell

33
Q

When the caps of the procollagen molecule are cleaved at exocytosis by enzymes in ECM, what is it now? Then what does it do?

A

Collagen Molecule

Molecules self-assemble end to end in rows and parallel rows cross link forming a collagen fibril

Collagen fibril contains parallel fibrils

34
Q

Where are collagen fibers degraded?

A
  1. In ECM
  2. Inside a fibroblast
35
Q

How are collagen fibers broken down in ECM?

A

Natural breakdown

Matrix metalloproteases

Cells may exocytose lysosome contens

36
Q

How are collagen fibers degraded in fibroblasts?

A

Fibroblast endocytosis part of collagen fibril via phagocytosis and degraded in a phagolysosome

37
Q

Matrix Metalloproteases

A

In ground substance

Proteolytic enzymes that collectively break down almost all ECM components

Breakdown necessary to maintain, remodel, and repair ECM

ECM remodeling is necessary for normal and essential tissue level processes

Collagenases - matrix metalloproteases that break down collagens I, II, or III

38
Q

What are the 3 main components of elastic fiber?

A

Elastin protein forms the core of an elastic fiber

Microfibrils of fibrillin glycoprotein surround and are partially embedded in the elastin core

Microfibril associated glycoproteins

39
Q

What is the function of elastic fibers?

A

Impart elasticity to ECM/tissue - initially accommodate tensile forces and when tension released, they return to their original shape and size

Abundant in tissues that need to stretch and return to original size/shape

40
Q

What does fibrillin do?

A

Help hold elastic fiber together

Connect fiber to the cell, ground substance, signaling molecules, other fibers, etc.

41
Q

Why do tissues lose elasticity with age?

A

Fibroblasts have relatively low turnover in adult and do less repair as they get older

42
Q

What is the difference between elastic fibers and collagen I fibrils/fibers?

A

Fewer crosslinks between adjacent elastin monomers

Cross links between elastin monomers are weaker

Cross links do not bind elastin as tightly as collagen and the arrangement of elastic molecules less uniform

43
Q

What do elastic fibers look like in LM?

A

Elastic fibers are slender and branched (Y shaped) and do not reticulate

Elastin stains react with the elastic protein component of elastic fibers

Acidophilic but hard to see in LM

44
Q

What is the function of ground substance?

A

Fills space between cells and fibers

Gel is a diffusion and exchange medium

Components drive ECM hydration

Hydrated ground substance resists compression

45
Q

What are the major components of ground substance?

A

Glycosaminoglycans (GAGs)
Proteoglycans
Multi-adhesive glycoproteins
Matrix metalloproteases (MMPs)

46
Q

Glycosaminoglycans

A

Each GAG is a long chain of repeating identical disaccharides

Strong negative ionic charge - usually sulfated and repeated carboxyl groups

Negative charge attracts osmotically active cations and this is turn attracts water

47
Q

Proteoglycans. What are their function and how can they appear in LM?

A

GAGs attached to central protein core

Function: Mega-Hydration and binding sites for growth factors and signaling molecules

LM: basophilic and metchromatic

48
Q

Multi-adhesive glycoproteins. What are the functions?

A

Linker proteins with at least 3 binding sites

Link up with at least one of each:
- cell adhesion molecules (CAMs) - often intergrins
- collagen fibers in ECM
- proteoglycans in ECM

Function: 3-way or more hookups link the cell to fibers and to ground substance in ECM. Promote adhesions between ECM and cell (stability and mechanotransduction)

49
Q

What occurs with inhibition of matrix metalloproteinases that promote angiogenesis in cancer?

A

Slow the growth and progression of some malignant tumors

FoundSci Unit 4 (11 decks)

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