extra cellular matrix Flashcards

1
Q

what is ecm

A
  • network of macromolecules that occupy extra cellular space eg. proteins, proteoglycans, minerals
  • secreted by cells
  • forms large % of connective tissue
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2
Q

what two main classes of macromolecules does the ECM of connective tissue

A
  • fibrous proteins
  • proteoglycans
  • water is also a major component
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3
Q

what are 5 roles of ecm

A
  • acts as a signal which influences cell function
  • stores and presents growth factor
  • acts as a scaffold for tissue repair
  • important in cell adhesion
  • establishes tissue microenvironment
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4
Q

ecm proteins - collagen

A
  • collagen is the most abundant protein in ecm
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5
Q

which two collagen types are the most abundant in ecm of connective tissues

A
  • type 1 and type 11 such as tendons, cartilage and bone
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6
Q

properties of type 1 and type 11 collagen

A
  • resist stretching and provide a structural framework and tissue strength to the tissues (tensile properties)
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7
Q

how many types of collagen

A
  • type 1, 2, 3, 4 (basal lamina - non fibrular) , 5 (less abundant)
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8
Q

elastin properties

A
  • low tensile strength
  • elasticity found in tissues such as lungs and arteries - this allows for them to be repeatedly stretched and undergo elastic recoil
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9
Q

what is fibronectin and its role

A
  • fibrous proteins found in ecm
  • has 2 forms; soluble form in blood, insoluble in cell
  • large dimer of 2 nearly identical proteins
  • main role in guiding the organisation and structure of ecm
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10
Q

what is laminin and its role

A
  • trimeric cross structure - sheet like
  • binding site for cells and other proteins
  • major component of basal lamina
  • mutations - nephrotic syndrome (kidney disease issue with filtration)
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11
Q

what roles are both laminin and fibronectin involved in

A
  • cell differentiation
  • cell migration
  • cell adhesion
  • they both can bind to both components of the ECM and intern receptors on plasma membrane of cells so anchoring the cell directly to ecm
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12
Q

what are proteoglycans

A
  • composed of a specific protein core structure to which long, unbranched polysaccharide chains are covalently attached
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13
Q

what is a glycosaminoglycan (GAG)

A
  • the polysaccharide side chains attached to the core protein are made up of repeating disaccharide units and are named glycosaminoglycans
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14
Q

some proteoglycans

A
  • contain one or two GAG and some have over 100
  • some GAG eg. keratin sulphate found in aggrecan are sulphated
  • this means that the proteoglycans can carry a dense negative charge and will bind to a water molecule to form a hydrated gel that resist compressive forces
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15
Q

in what three ways are proteoglycan classified as

A
  • according to their core protein
  • localisation
  • GAG composition
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16
Q

ecm mineral

A
  • ecm can be mineralised

- calcium hydroxyapatite gives tough, hard mechanical properties

17
Q

basement membrane role

A
  • specialist ecm
  • network of macromolecules
  • cell attachment - separates epithelium and connective tissue
  • gives cell signal to divide
  • important in filtration in kidney
18
Q

how do cells interact with the ecm

A
  • cells can interact with the ecm through specialised membrane bound receptors (integrins)
  • specific dimer pairing determines ligand binding
  • mediates cellular effects
  • bidirectional signalling molecules
19
Q

how do cells modify the ecm

A
  • cell can modify the ecm
  • such as proteolytic enzymes - degrade the ecm
  • release/activates growth factors
  • altered expression in wound healing
20
Q

wound healing process

A
  • matrix forms structure for skin
  • when wounded signalling changes
  • fibrin acts as a signal to repair skin
  • matrix changes
  • granulation tissue forms to heal
  • structure of skin formed
21
Q

integrins in cancer

A
  • ecm and integrin expression is changed in cancer
  • integrin signalling influences cell growth, cell migration and anoikis
  • targeting ecm and integrins in anti cancer therapy and imaging
22
Q

ecm mechanics

A
  • ecm can exist with different stiffness and elasticity
  • dependent on composition
  • affects cell behaviour
  • integrins can acts as mechanosensors
  • stiffness changes in disease
23
Q

in order for new tissue to replace damaged tissue

A
  • need to know molecules, mechanics of tissue, soluble signals