Lamellipodial extension driven by actin assembly

Rac-GTPase

Cell spreading and migration require myosin activity

lamellipodia

lamella

Pollard T.D. and Borisy G.G., 2003, Cell, 112:453-65

Svitkina T.M. and Borisy G.G.,1999, J Cell Biol, 145:1009-26

Forces generated by Myosins?

actin plolymerization (front) and depolymarization (rear)

define the lamellipodial width

Contraction

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Release

Recycling

Force Force

Attachment

Contraction

Extension

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Cell migration: a cyclic process of force generation

1. lamellipodial extension:forward force exerted by actin

polymerizationon the membrane

2. extracellular matrix probing:rearward force exerted by actin flow

on integrins

How the cell locally transduces

the rigidity of the ECMinto a contractile signal

used to direct lamellipodial extension?

Sheetz M.P., Felsenfeld D.P., Galbraith C.G., 1998, Trends Cell Biol, 8:51-4

Neural Crest Migration

• The peripheral nervous system is created by a spatiotemporally co-ordinated migratory process during which the precursor cells, the neural crest (NC) cells, traverse the embryo to reach distantly located sites.

• Homing of peripheral neurons and their supportive cells might be dictated by a delicate equilibrium between the multiple actions of stimulatory and inhibitory molecules, which is modulated further by defined responses of the dispersing cells to these ECM components during their successive phases of phenotypic diversification.

Extracellular Matrix-Integrin Interactions in Motility and Signaling

Matrix molecules are typically bound by integrins

Integrins are alpha-beta dimeric membrane proteins needed for motility, signal, and force transduction.

Antibodies to integrins block cell migration and spreading

Integrin Knockouts have Severe Phenotypes

Further Roles for Integrins

Steps In NC Migration

• Initiation of migration

• Migration

• Homing

• Differentiation

Rigidity of Matrix Directs Motility

Initiation of Migration

• Transition from tissue ball to migration

• Loss of cadherins

• Acquisition of Integrins

• Acquisition of motile machinery

• Stimulus to migrate

Important Aspects of Migration

1. Isovolumic

2. Constant Membrane Area

3. Actin filament assembly and disassembly

4. Actin filament contraction

5. Matrix binding

6. Matrix Rigidity

7. Release of matrix binding

Attachment and Contraction

Matrix Forces Directed Inward And Balanced

nucleus

front

Tra

cti

on

(n

N/

m2

)

4

3

2

0

-1

-2

-3

-4

1

cell direction

time

rear tail

rear-endo-plasm

nuclearregion

ecto-plasm /lamella

front-endo-plasm

lamelli-podium

rearward

for-ward

Traction

How does a cell treat the ECM?• Movie 2: One cell deforms a collagen fibre

QuickTime™ and aVideo decompressor

are needed to see this picture.

Contraction

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Release

Recycling

Force Force

Attachment

Contraction

Extension

Recycling

Release