Deze samenvatting bevat alle onderwerpen behandeld tijdens het master vak BMS756- Cell motility in physiology and pathology (actin organization/dynamics, polarization, protrusion, adhesion, contraction, tail retraction, environmental guidance of cell movement, haptokinesis, haptotaxis, chemotaxis, ...
, BMS76 – Cell Motility in Physiology and Pathology
Content
Intracellular mechanisms of cell movement......................................................................................4
Molecular mechanisms of actin organization as driver of migration...................................................................4
Molecular actin filament organization/dynamics...........................................................................................4
Mechanisms of filament assembly..................................................................................................................5
Environmental guidance of cell movement and modes of migration.................................................7
Environmental guidance of cell movement..........................................................................................................7
Haptokinesis as environmental guidance mechanism for cell migration.......................................................7
Taxis as environmental guidance mechanism for cell migration....................................................................7
Cell migration modes and transitions...................................................................................................................8
Single amoeboid..............................................................................................................................................8
Single mesenchymal........................................................................................................................................8
Cell migration in wound healing and morphogenesis......................................................................10
Steps of wound healing.......................................................................................................................................10
Signaling pathways involved and cell migration strategies................................................................................10
Experimental approaches to study wound healing.............................................................................................11
Scratch assay.................................................................................................................................................11
Lens ex vivo wound repair model.................................................................................................................11
Normal vs. chronic wound..................................................................................................................................12
Morphogenesis....................................................................................................................................................12
Cell migration in immune defense and angiogenesis.......................................................................13
Protrusion-based migration in immune cells......................................................................................................13
Cell migration in angiogenesis.............................................................................................................................14
Migrating cells in cancer..................................................................................................................14
The metastatic cascade.......................................................................................................................................14
Plasticity of invasion programs...........................................................................................................................15
Organ colonization..............................................................................................................................................16
Migrating cells in inflammation and immunotherapy......................................................................17
Principles of leukocyte recruitment into tissues and cell-cell interaction..........................................................17
Immunotherapy in cancer...................................................................................................................................17
2
, BMS76 – Cell Motility in Physiology and Pathology
iRATs...............................................................................................................................................19
iRAT Week 1: Basic mechanisms of cell movements..........................................................................................19
iRAT Week 2: Cell migration in physiology..........................................................................................................21
iRAT Week 3: Cell migration in disease...............................................................................................................23
3
, BMS76 – Cell Motility in Physiology and Pathology
Intracellular mechanisms of cell movement
Molecular mechanisms of actin organization as driver of migration
Mesenchymal migration is a mode of cell movement where cells with a fibroblast-
like shape move through a tissue matrix. It occurs in several steps:
1. Polarization: The cell establishes a "front" and "back," setting a direction
for movement.
2. Protrusion: The cell membrane extends at the leading edge. Actin
filaments push the membrane outward, forming structures that help the
cell explore and anchor the ECM.
3. Adhesion: Stable attachments form between the cell and the ECM.
Integrin proteins cluster at focal adhesions, providing anchor points for
traction.
4. Contraction: The cell body moves forward. Myosin motor proteins pull
actin filaments at the rear, contracting the cell and advancing it.
5. Tail retraction: The cell’s rear detaches, completing the movement cycle.
Rear focal adhesions dissemble, allowing the cell to move forward freely.
Molecular actin filament organization/dynamics
Actin monomers (G-actin) assemble into dynamic filaments (F-actin)
through a process regulated by ATP. When G-actin monomers bind ATP,
they are more likely to join the growing "plus" (barbed) end of an actin
filament, promoting elongation. Once incorporated, actin’s ATPase
activity hydrolyzes ATP to ADP, which stabilizes the filament but
gradually reduces the affinity of actin subunits for each other. At the
opposite "minus" (pointed) end, older ADP-bound actin monomers
disassemble more readily. This polarized assembly leads to a
phenomenon called treadmilling, where ATP-actin monomers add at
the plus end while ADP-actin monomers disassemble at the minus end,
allowing the filament to maintain a steady length while
continuously cycling monomers through.
Profilin: binds to G-actin monomers, enhancing their ability to
bind ATP and directing them toward the barbed end, thus
promoting filament elongation.
Cofilin: binds to ADP-actin subunits within older segments of
the filament, inducing a conformational change that increases
the rate of disassembly at the pointed end.
There are several inhibitors that specifically target actin
polymerization and depolymerization:
Phalloidin: This compound binds tightly to F-actin,
stabilizing actin filaments and preventing their
depolymerization.
Jasplakinolide: Jasplakinolide promotes actin
polymerization by stabilizing F-actin and enhancing
nucleation, the initial step of filament formation. This
leads to excessive actin polymerization and a rigid actin
network that resists normal depolymerization.
Cytochalasin D: By binding to the barbed (plus) end of
actin filaments, cytochalasin D prevents the addition of
new actin monomers.
Latrunculin A: This inhibitor binds to G-actin monomers,
preventing them from incorporating into F-actin.
4
Voordelen van het kopen van samenvattingen bij Stuvia op een rij:
Verzekerd van kwaliteit door reviews
Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!
Snel en makkelijk kopen
Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.
Focus op de essentie
Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper StudentRU07. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor €7,99. Je zit daarna nergens aan vast.
