extra cellular matrix

Question 1

what is ecm

Answer 1

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

Question 2

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

Answer 2

• fibrous proteins
• proteoglycans
• water is also a major component

Question 3

what are 5 roles of ecm

Answer 3

• 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

Question 4

ecm proteins - collagen

Answer 4

• collagen is the most abundant protein in ecm

Question 5

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

Answer 5

• type 1 and type 11 such as tendons, cartilage and bone

Question 6

properties of type 1 and type 11 collagen

Answer 6

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

Question 7

how many types of collagen

Answer 7

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

Question 8

elastin properties

Answer 8

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

Question 9

what is fibronectin and its role

Answer 9

• 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

Question 10

what is laminin and its role

Answer 10

• 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)

Question 11

what roles are both laminin and fibronectin involved in

Answer 11

• 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

Question 12

what are proteoglycans

Answer 12

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

Question 13

what is a glycosaminoglycan (GAG)

Answer 13

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

Question 14

some proteoglycans

Answer 14

• 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

Question 15

in what three ways are proteoglycan classified as

Answer 15

• according to their core protein
• localisation
• GAG composition

Question 16

ecm mineral

Answer 16

• ecm can be mineralised

- calcium hydroxyapatite gives tough, hard mechanical properties

Question 17

basement membrane role

Answer 17

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

Question 18

how do cells interact with the ecm

Answer 18

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

Question 19

how do cells modify the ecm

Answer 19

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

Question 20

wound healing process

Answer 20

• 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

Question 21

integrins in cancer

Answer 21

• 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

Question 22

ecm mechanics

Answer 22

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

Question 23

in order for new tissue to replace damaged tissue

Answer 23

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