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Remodelling Flashcards

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AP® Biology flashcards Biology 101 flashcards
1
Q

how can cells behave as communities?

A
  • different cell types interact
  • make larger structures tissues and then organs
  • allows/enables organisms
  • ECM allows tissues to form
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2
Q

what is the ECM?

A
  • extracellular matrix
  • forms a home for cells
  • fibres surround cells
  • interact with ECM through integrins
  • eg collagens, fibronectin, iaminium, proteoglycans
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3
Q

what are tissues composed of?

A
  • cells and often ECM

- epithelial doesnt have it

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4
Q

what is the ECM composed of?

A

different proteins and proteoglycans

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5
Q

what does the composition of ECM determine?

A

determines the physical properties from hard structures

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6
Q

what is the role of the ECM?

A
  • not just an inert scaffold, its dynamic
  • helps to define the phenotype and behaviour of the cell
  • acts as a storage compartment for signalling molecules
  • regulates what signals are presented
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7
Q

what are some features of collagen?

A

around 25% of the total mammalian proteins

  • vitamin c is an essential cofactor for collagen synthesis
  • around 30 different types
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8
Q

what is the strutcure of collagen?

A
  • composed of homo or heterodimers of alpha chains to form a triple helical based structure
  • amino acid sequence consists of Gly-x-4
  • divided into fibrillary or non-fibrillar
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9
Q

what are fibrillar collagens?

A

organised into fibres and provide tensile strength

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10
Q

what are non-fibrillar collagens?

A

collagens form networks and sheet like structurs

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11
Q

how is collagen organised?

A
  • amino acid chain
  • alpha chain
  • assembled into triple helices
  • assembled into collagen fibrils
  • finally into collagen fibres
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12
Q

why does collagen need gly in the amino acid chain?

A
  • ensures every third residue can twist to form the alpha helix
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13
Q

what is the triple helix?

A

assembly end to end to make an elongated structure and join through covalent bonds

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14
Q

how is collagen synthesised?

A
  • initally in the cell but then outside
  • ribosome = synthesis of alpha chains (has a pro-peptide domain that can be later cleaved off)
  • vitamin C interacts and enables hydroxylation of selected prolines and lysines
  • glycosylation events occur in the ER
  • assemble into the triple helices aided by disulphide bonds
  • packaged into a vesicle and secreted out of the cell
  • pro-callgen contains the pro-peptide domain
  • cleavage of pro-peptides through pro-collagen peptidases
  • get collagen allowing assembly into a collagen fibril
  • then aggregates into the fibre
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15
Q

what is brittle bone disease?

A
  • osteogenesis imperfecta
  • mutations in alpha1 or alpha2 genes
  • clearest symptom is bone fragility
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16
Q

what is dermatosparaxis?

A
  • proteolytic processing of procollagen is require for correct assembly into fibrils
  • fragile and loose skin with substantial bruising and bleeding
  • caused by mutation in the N terminal pro-peptides
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17
Q

how do glycosaminoglycans and proteoglycans interact?

A

glycosaminoglycans (GAGs) are covalently attached to a core protein to form proteoglycans (except hylauronan)

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18
Q

what do glycosaminoglycans and proteoglycans?

A

provide hydrated, space-filling functions and compressive strength

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19
Q

what are GAGs?

A
  • 4 classes
  • formed by polymerisation of specific disaccharides and modification
  • chrondroiton sulfate, hepara sulfate and keratan sulfate (attach to core proteins)
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20
Q

what are hyaluronans?

A

can attach to the proteoglycan aggrecan or exists as its own disaccharide polymer

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21
Q

what are some examples of proteoglycans?

A

aggrecan (CS KS), Decorin (CS DS), Perlecan, Syndecan

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22
Q

what is the process of assembly of GAGs and proteoglycan?

A
  • a core protein to which GAGs attach
  • sequential addition of GAGs and linking sugars
  • have repeating disaccharide repeats

GAGs –> Sugars –> Core protein

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23
Q

how does hyaluronan bind?

A
  • bind to the aggrecan

- does that through its N terminal hyraluronan binding domain and links proteins

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24
Q

how are GAGs and proteoglycans involved into cell signalling?

A
  • proteoglycans can regulate cell signalling events
  • have a major role in signalling between various secreted signalling molecules
  • can inhibit or enhance the signalling activity of growth factors
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25
Q

what is FGF signalling?

A
  • fibroblast growth factor
  • syndecan is a heparan sulfate proteoglycan (HSPG) that helps to control FGF signalling strneght - membrane bound
  • Free FGF can bind heparin sulfate side chains
  • syndecan can determine the concentration of FGF at the cell surface
  • can have free heparin sulfate proteoglycans
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26
Q

what is the role of elastin?

A
  • maintains the elasticity in the skin
  • provides elasticity to help regulate tissue function
  • allows stretching
  • consists of covalently linked monomers
  • when relaxed has a coiled sturcture
  • found in the lungs and elastic ligaments
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27
Q

what is curtix laxa?

A
  • mutations that effect how elastic is produced or organised
  • rare inherited disorder
  • skin inelastic and hangs loosely, hypermobility of the joints may also feature
28
Q

what is fibronectin?

A
  • large glycoprotein that helps matrix organisation
29
Q

what is the role of fibronectin?

A

helps matrix organisation

- has a specific binding domains that can link thing together

30
Q

what is the structure of fibronectin?

A
  • has a very specific binding domain

- homodimer has binding motifs for proteoglycans, cells and collagen

31
Q

how can you see cells grown on different fibronectin shapes?

A
  • determines how cells adhere to structures by presenting one surface to ahere to
  • a teardrop FN
  • when the cell is on the FN it occupies the space available
  • a lemellipodium forms
  • produces structure for migration
  • can grow on different shapes
  • from this can determine how structures in the cell are organised
32
Q

what is the basement membrane?

A
  • specific ECM barrier
  • separates the epidermis and the dermis
  • above = has keratinocytes
  • bellow = collagen network in underlying dermis
  • a flat, sheet structure
33
Q

what is the basement membrane composed of?

A
  • entactin, perlecan, laminin, IV collagen
34
Q

what is entactin?

A

multi-adhesive matrix protein

35
Q

what is type IV collagen?

A
  • non-fibrillar collagen
36
Q

what is the structure of Type IV collagen?

A
  • triple helical with a C terminal globular domain and N terminal domain
  • assemble end to end and laterally
  • globular heads come together to form alpha helices
  • organise into the alpha helix
  • collagen dimerisation through C-Nc trimers
  • head to head interactions
37
Q

what does the basement membrane act as?

A

a selective barrier for cell molecules

38
Q

what are the properties of a stem cell?

A

to renew and differentiate

39
Q

what is self-renew?

A
  • asymmetric cell division
  • one becomes a differentiated cell
  • one becomes a stem cell
  • maintains the stem cell pool
40
Q

what is the telomerase activity like in stem cells?

A
  • high levels in stem cell
  • telomerase added back on the chromosome so its not shortening
  • especially in pluripotent
41
Q

what is totipotent?

A
  • have the ability to develop into an entire organism
  • very early days of embryogenesis
  • fertilised egg up until around day 4 (when the blastocyst is formed)
42
Q

what is pluripotent?

A
  • have the ability to develop into virtually every cell type
  • do norm form a placenta and supporting tissues
  • ES cell of the inner cell mass (ICM) in the blastocyst are pluripotent
43
Q

what does a teratoma assay determine?

A

the pluripotency

44
Q

how does a teratoma assay work?

A
  • inject into the back of mice

- remove an look for a teratoma which should include all 3 germ layers

45
Q

what are the 3 germ layers?

A
  • endoderm
  • mesoderm
  • ectoderm
46
Q

what transcription factors is pluripotency controlled by?

A
  • Oct-4
  • Nanog
  • Sox2
47
Q

what are the roles of Oct-4, Nanog and Sox2?

A
  • act collectively to regulate ESC pluripotency
  • can activate promoters of self-renewal genes
  • silent promoters of developmental genes
  • different genes can drive different specific lineage commitment pathways
48
Q

what is the therapeutic potential of stem cells?

A
  • generation of specific cell types and tissue structures to replace worm or disease body parts
  • eg neurodegenerative, disease, diabetes corneal defects, cardiovascular disease, musculoskeletal disorders
49
Q

what are the potential difficulties of stem cells as a therapy?

A
  • understanding how specialisation takes place

- directing differentiation to generate specific tissue types

50
Q

how stem cells been used in experimental therapies for Parkinson’s disease?

A
  • directed differentiation of dopaminergic neurons
  • NURR1, FGF8 and shh are all required in the normal brain
  • look at markers to see if shh and FGF8 have the same markers as DA neurons (this doesnt tell you about functionality)
  • then did an in vivo model in a mice model
  • DA neurons killed
  • test if functions are recovered by transplanted cells
51
Q

how could ES cells be used to treat paralysis?

A
  • differentiated into cells in the spinal cord
  • rat recovered to some extent
  • some ability to walk
52
Q

what is SCNT?

A
  • somatic cell nuclear transfer

- fusion of a somatic cell nucleus with an egg emptied of its genetic material

53
Q

how can SCNT be used in therapies?

A
  • therapeutic cloning, generate a blastocyst where pluripotent cells are expanded in vitro
  • used to create dolly the sheep
54
Q

what are adult stem cells?

A
  • they are multipotent
  • many tissues in the adult can undergo repair and remodelling
  • enabled by the presence of stem cells
55
Q

what is multipotent?

A

differentiate into more than one cell type

  • much more restricted
  • generates cells of the tissue in which it resides
56
Q

how can multipotent stem cells be used therapetuically?

A
  • patients own cells can be used
  • fewer ethical concerns as not using embryos
  • fewer safety concerns as a teratoma wont be formed
57
Q

what are heamatopeoitic stem cells used in?

A
  • bone marrow transplants and blood transplants

- the rate of these kind of transplants are generally increasing

58
Q

what are mesenchymal stem cells?

A
  • found in the bone marrow
  • differentiate to bone, fat and cartilage
    (make osteoblasts, chondrocytes, adipocytes and stromal cells)
59
Q

where are mesenchymal stem cells targeted>

A
  • at disorders that affect the muscoskeletal system
  • can make bone and cartilage
  • theoretically be used to regrow
  • studies have been successful to some degree
60
Q

how can cornea and limbal stem cells be used?

A

treat the epithelial structure on the outer surface

- eg when theres a limbal cell deficiency or a chemically burnt eye

61
Q

what is the limbus?

A
  • round the outside of the cornea
  • stem cell niche
  • migrate to the epithelial layer which is essential for protecting the cornea
62
Q

how would loss of corneal function be treated with stem cells?

A
  • limbal harvest
  • limbal stem cell culture (explant culture or suspension culture)
  • culture limbal epithelium on a scaffold
63
Q

what are iPS cells?

A

induced pluripotent stem cells

- can express telomerase, ESC surface markers and differentiate into the 3 germ layers

64
Q

how can iPS cells be used?

A
  • introduction of genes associated with ESC pluripotency
  • can reprogramme somatic cells to pluripotent stem cells
  • introduction of just four factors appear to be sufficient
65
Q

what are the issues with iPS cells?

A
  • reprogramming somatic cells to iPS is inefficient
  • use of viral delivery systems
  • use of oncogenes (potentially cancer forming)
  • epigenetic memory of parent cells
  • teratoma risk
66
Q

what are the potential of iPS cells?

A
  • differentiate cells into whatever we need
  • personalised medicine
  • transplants

Cell Biology (10 decks)

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