Cell Adhesion Flashcards
How to cells transmit physical stresses?
i) extracellular matrix
ii) cytoskeleton and cell-cell adhesions that connect the cytoskeletons of neighbouring cells
plants use ECM
animals use both in different tissue types
What is the most common additional polymer in the secondary cell wall?
lignin
What gives the wall its tensile strength?
cellulose microfibrils, composed of ~16 cellulose molecules with each molecule being made of 100s of glucose subunits
found in plants
What are some roles of pectin?
provides resistance to compressive forces
highly hydrated, binds cations
space filling effect
crosslinks w cellulose to form a matrix
found in plants
Where are cellulose microfibrils predominantly found?
secondary cell wall
Where is pectin abundant?
primary cell walls
What is the function of the middle lamella?
cements primary cell walls of adjacent plant cells together
What molecule is the middle lamella abundant with?
pectin
What are some properties of lignin?
complex polymer of crosslinked phenolic compounds
high wet strength (rigid when wet)
How is cellulose synthesised?
by the cellulose synthase complex which is physically linked to underlying microtubules which guide the enzyme complex
What are the bone forming cells that secrete collagen matrix?
osteoblasts
What are osteons?
a collection of concentric rings composed of mineralised matrix deposited around a central canal containing blood vessels and nerves
What is hydroxyapatite composed of?
calcium, magnesium and phosphate ions
What is collagen and where is it found?
protein molecules made up of amino acids
provides structural support to the extracellular space of connective tissues
found in skin, tendons, bones, and ligaments
What are some properties of cartilage?
found in many joints
strong, flexible
large amounts of ecm (collagen)
no mineralisation
~25% total protein mass in a mammal
>40 collagen genes in mammals
Where is the vitreous humour found and what is it?
between lens and retina in the eye
clear, viscous gel
composed of water, collagen, hyaluronic acid
virtually acellular
What is an example of a collagen-producing cell?
fibroblast
What is the sequence of collagen organisation?
monomer -> trimer -> fibril -> fibre
How is collagen arranged in skin?
plywood like pattern allowing resistance to tensile stress in multiple directions
How is collagen arranged in tendons?
tendons attach muscle to bone
collagen fibres align in parallel, along axis of extension
How do fibroblasts influence the alignment of collagen fibres?
they pull on and shape the collagen they have secreted
fibroblasts at the end of a wound become migratory to close the wound
In what form is collagen secreted
procollagen, which has additional peptide extensions that obstruct premature fibril assembly
How does procollagen form collagen?
procallagen proteinases cleve terminal extensions
the new mature collagen molecules self assemble into collagen fibrils outside of the cell
What is the primary function of fibronectin and integrins?
help cells attach to the ECM
fibronectin acts as a molecular bridge between integrins and the ecm
What do integrins exist as?
heterodimers with alpha and beta subunits
What is the structure of fibronectin?
exists as a homodimer bonded by disulphide bonds at one end
has a cell attachment site eg via integrin
has an ecm binding site eg via collagen
How are integrins regulated?
by signals form inside and outside the cell which can make integrins active or inactive
on/off integrin connections w ecm allow cells to move through tissue
What are some roles of glycosaminoglycans (GAGs)?
negatively charged so draw in water which creates swelling pressure
swelling pressure balances tension in collagen fibres
also keeps high [cation] in ECM
space fillers in connective tissue
How are proteoglycans structured?
chains of GAGs linked to a core protein which can form v large aggregates
resistant to compression
What are some roles of proteoglycans?
binding growth factors
control of migration of cells through ecm
What is the epithelium and what is its role?
it is a sheet of cells joined side by side that covers external surfaces and line all internal cavities
creates barriers and controls movement of molecules in and out
protects against microbes and fluid loss
has polarity
What types of epithelial cells are there and what are their functions?
columnar: secretion/filtration
squamous: filtration
cuboidal: secretion/absorption
stratified: protection
What is the structure which the epithelial sheet sits on?
a mat-like structure called the basal lamina, a thin tough sheet of ecm
what is the role of the basal lamina?
separates the epithelial cells from the network of collagen fibres in the underlying connective tissue
What is the basal lamina composed of?
type IV collagen supplied by underlying stromal cells
laminin supplied by overlying epithelial cells
What is the function of laminin?
provides adhesive sites for integrins located in the basal membrane of epithelial cells
Epithelial cells have two faces, what are they?
apical surface -is exposed to air or bodily fluids
basal surface - is attached to basal lamina
What is the function of tight junctions?
tightly binds epithelial cells together
blocks diffusion of membrane proteins to keep apical and basal domains of cell separate
How do tight junctions transport glucose?
transports glucose against its concentration gradient (sodium driven transporter) in from the gut lumen and the down its concentration (passive transporter) out into the bloodstream
What are adherens junctions?
cadherins (calcium-dependent adherence proteins) join actin filaments (cytoskeleton) of neighbouring cells providing mechanical strength
What are desmosomes?
connect keratin filaments (an intermediate filament) in neighbouring epithelial cells
contains cadherins (different set than adherens junctions)
found in tough and exposed skin
What are hemidesmosomes?
join keratin filaments in the epithelial cell membrane to basal lamina
Where are adherens junctions usually found?
near apical cell surface, just below tight junctions
What is an adhesion belt
a continuous belt of actin cytoskeleton across the epithelia sheet connected between adherens junctions
How can epithelial sheets change shape?
by organised tightening of adhesion belts
What is the cause of spina bifida?
when the neural tube does not close properly due to adhesion belts not tightening correctly
What are gap junctions?
small regions of plasma membrane where two cells are v closely apposed in parallel
allow small intracellular molecules to travel from cell to cell
gated, can be regulated by extracellular signals eg retinal neurons close in response to dopamine
How are gap junctions formed?
connexin protein complexes in the plasma membrane of each cell line up to form a waterfilled channel between the two adjacent cells
How are gap junctions important in the function of the heart?
molecular flow creates an electrical and mechanical coupling between cells
allows waves of electrical stimulation to spread synchronously through the heart
triggers coordinated contraction of cardiac cells that produce each heartbeat
What are plasmodesmata?
perform the role of gap junctions in plants
plants lack tight junctions, adherens junctions, desmosomes and hemidesmosomes
What are three types of cadherin and where are they expressed?
e-cadherin: mainly expressed on epithelial cells
n-cadherin: expressed on nerve, muscle, and lens cells
p-cadherin: expressed in placenta and epidermis
What is compaction and when does it occur?
occurs at 8-cell-stage mouse embryo development
e-cadheren forms adherens junctions
e-cadheren localised to basolateral cell-cell contact sites
How do cadherins perform homophilic adhesion?
have n and c terminus ends, where N is the hinge region that allows structure to sense microenvironment
calcium ions bind to hinge regions and lock the structure/conformation when bound to another cadherin
Why is it important that individual cadherin-cadherin interactions are weak
because cell-cell interactions break and reform during embryo development and in adult tissues
How do cells selectively assemble?
levels of cadherin expression affects affinity of cell-cell interaction
cell w higher cadherin levels form stronger interactions.
Cells with higher cadherin levels are more tightly packed into the centre of the assembly.
What is EMT?
Epithelial-to-Mesenchymal Transition
reversible reaction
found in developing tissues
involved in cancer cell invasion
mesenchymal cell are more motile and express more n-cadherin
What is carcinoma?
cancers arising from epithelial cells
accounts for ~80% of cases
What are selectins?
cell-surface proteins that bind carbohydrates
expressed in white blood cells and endothelial cells
linked to actin cytoskeleton
mediate transient cell-cell adhesions in the bloodstream
What are the different types of Leukocyte Adhesion Deficiency (LAD) disorders?
LAD-I: integrin absent - defective tight adhesion and rolling
LAD-II: glycosylation effect on selectin ligands - defective initial binding and rolling
LAD-III: integrin activation defect - defective tight adhesion and invasion
What are the two main groups of ECM-degrading enzymes?
matrix metalloproteinases (MMPs): require bound Ca2+ or Zn2+ for activity
serine proteases: have conserved serine residue in active site
highly substrate specific
Why is remodelling of ECM important?
to allow space for migrating cells
eg infiltrations of tissue by white blood cells
Give examples of ways in which some proteases are controlled.
secreted in an inactive form
confined by cell-surface receptors
inhibited by actions of locally secreted inhibitors eg tissue inhibitors of metalloproteinases (TIMPs)
How do cells transmit physical stresses?
i) extracellular matrix
ii) cytoskeleton and cell-cell adhesions that connect the cytoskeletons of neighbouring cells
plants use ECM
animals use both in different tissue types
How do cancer cells break through the ECM?
through the use of enzymes, proteolytic ECM degradation
force mediated breakage led by myofibroblasts which bind to integrins which breaks basal lamina
How do white blood cells invade tissue?
selectins initiate weak binding and rolling
selectin at surface of endothelial recognise sugar on white blood cells
leukocytes then activate integrins, which recognise endothelial membrane proteins
integrins mediate stronger adhesion and tissue invasion of white blood cells (stage 2)
binding is stronger near site of infection, white blood cells squeeze through endothelial cells
Which proteins seal interacting cells in tight junctions?
Occludin and Claudin
