BIO 211 Lecture 10 Cytoskeleton Forces and Cell Movement

metastasis

When cell migration goes wrong, — can occur

Mesenchymal

— cells are strongly connected to the surrounding environment

• Single cell migration

• Fibroblasts

Amoeboid

— cells are connected by loose adhesions and are much less adherent to their environment

Blebbing

— is a form of cell migration that is not actin dependent

pressure

Blebbing relies on —

slow

Mesenchymal cell migration is —

fast

Amoeboid cell migration is —

Integrins

a family of transmembrane receptor proteins that facilitate cell-extracellular matrix (ECM) adhesion and cell-cell interactions

extracellular

The — domain of integrins binds to ligands like fibronectin, collagen, and laminin in the ECM

cytoplasmic

The — domain of integrins interacts with intracellular signaling molecules and cytoskeletal proteins.

Actomyosin

the complex formed by actin filaments and myosin motor proteins, playing a crucial role in muscle contraction and cellular motility

front, back

In migration, new adhesions are formed at the — of the cell and old adhesions are broken at the — of the cell

chemotaxis

the movement of cells or organisms in response to a chemical gradient

collagen

integrins bind to — in the connective tissue ECM

heterodimer

integrin is a — composed of an alpha and a beta subunit

intracellular tails

the — of integrins are hotspots of intracellular signaling and cytoskeletal dynamics

positive

Adhesion maturation is a — feedback loop

ECM binding site

An integrin needs to be activated in order to expose the —

GTPase

A small — and RIAM activates the integrin

Talin

A cytoskeletal protein that directly binds to integrins, promoting their activation and linking them to the actin cytoskeleton. It plays a fundamental role in focal adhesion formation and force transmission.

Vinculin

A mechanosensitive protein that reinforces integrin-actin connections by binding to talin and actin. It stabilizes focal adhesions and enhances adhesion strength in response to mechanical forces.

Kindlin

A co-activator of integrins that works alongside talin to promote integrin activation. It is essential for integrin-mediated cell adhesion and is implicated in various signaling pathways

Activated

1. Integrins become — and bind to talin and kindlin

2. Talin recruits vinculin, an adaptor protein that links the integrin complex to pre-existing actin filaments

3. The application of force to the integrin-actin complex recruits additional vinculin and actin filaments

Talin

— directly binds to integrin β-subunits at focal adhesions, promoting integrin activation

vinculin

Talin recruits and binds —, strengthening the connection to actin and increasing adhesion stability

vinculin

1. Integrins become activated and bind to talin and kindlin

2. Talin recruits —, an adaptor protein that links the integrin complex to pre-existing actin filaments

3. The application of force to the integrin-actin complex recruits additional vinculin and actin filaments

force

1. Integrins become activated and bind to talin and kindlin

2. Talin recruits vinculin, an adaptor protein that links the integrin complex to pre-existing actin filaments

3. The application of — to the integrin-actin complex recruits additional vinculin and actin filaments

talin activation

the force dependent trigger for positive feedback loop of adhesion maturation

vinculin

As talin unfolds, it exposes — binding sites

talin, vinculin

When actin filaments are pulled by myosin motors inside the cell, the resulting tension stretches the — rod, thereby exposing — binding sites.

• The vinculin molecules then recruit and organize additional actin filaments. Tension thereby increases the strength of the junction

fall

Some nascent adhesions — apart

back

At the — of the cell, adhesions go away

• If they don’t go away, the cell stretches until it stalls

• Breaking apart adhesions is critical for migration!

plasma membrane cortex

Contractility at the back of the cell is within the —

• As actomyosin contracts, it takes the plasma membrane with it

• Physically drags it out of adhesions

backwards

As actin networks polymerize at the front, if those networks aren't attached to anything in the cell, it would push the whole network — off the plasma membrane!!

focal adhesions

Cell attaches to pillars through —

• Forces are transmitted to pillars

• See traction forces that are transmitted from the stress fiber network via integrins

microtubules

— steer the cell

• Direction determined by where + ends go

plus (+)

Where the microtubule — ends go, the rest of the cell follows

deliver signals

Microtubule + ends — to the leading edge, direct actin polymerization, and adhesion formation

polarized

Traffic from the golgi is —

front

• Rac and Arp2/3 are only active at the — of the cell

  • Microtubule + ends help to activate Rac/Arp2/3 at only the front of the cell

  • Allow for new membrane protrusion and new adhesions

actomyosin

When — contracts, it pulls on the plasma membrane, causing retraction

cofilin, back

— is enriched at the leading edge

• Doesn't extend right up to the front of the cell

• Tends to be at the — of the leading edge network

• The great recycler

• Dynamic

cofilin

— maintains the actin monomer concentration at the leading edge

Rac1

— at the front causes protrusion

RhoA

— controls cortical contractility that leads to rear retraction

cortical actin contractility

RhoA controls — that leads to rear retraction

suppresses

Where Rac1 is active, it actively — RhoA signaling while also forming lamellipodia

suppressed

Where RhoA is active, lamellipodia formation is — as well as causing retraction

PAK

Rac1 activates —, which turns off the RhoA pathway

Arp2/3

Rac1 activates —, which drives lamellipodia formation

ROCK

RhoA activates —, which activates LIM kinase that inhibits cofilin, turning off the Rac1 pathway

ROCK

— activates LIM kinase and MLC(P)

LIM kinase

— is activated by ROCK and inhibits cofilin, which inhibits the Rac1 pathway

Rac1

Inhibition of cofilin inhibits the — pathway

MLC (P)

— activates increased myosin activity, leading to more stress fibers

PIP3

— activates Rac1

GPCRs

In chemotaxis, a bacterium releases a chemoattractant that binds to — on the cell surface

Gai

— dissociates from Gby, which goes on to activate PI3K

Rac GEFs

PI3K phosphorylates PIP2 to PIP3, which is a docking site for —

Ga12/13

— exchanges GDP for GTP on RhoA

drops

Blebs cease when the pressure of the cell —

nuclear lamina

SUN-domain proteins connect to the —

linker proteins

KASH-domain proteins attach to —