Unit 10: Cell Motility

Types of Cell Motility

1. Flagellar or Cilia dependent Swimming

2. Actin dependent migration

3. Amoeboid motion in a nematode sperm, no actin

Cells used for cell motility species

General: epithelial, mesenchymal
Specialized: neurons, immune

Systems Level Analysis

• breaks down system into a set of inputs, core processes, and outputs

• inputs and outputs are specific

• core processes are shared by different cells and pathways

Signals and Responses

Signals from outside: chemical, neighbor cells, mechanics, electrical, and photo

Responses inside the cell: new phenotype, new gene expression, cell movement or shape change, cell cycle, and apoptosis

Movement of cells can..

1. be driven by cytoskeleton and associated motor proteins

2. be coordinated and are responsible for building structures and organs

How does Cell Motility work?

Cell Shape and Locomotion:
1) Cell polarization (in yeast cells)
2) RNA localization
3) Plasma membrane protrusion
4) External signals guide cell migration
5) Cell examples: Keratocytes and Neurons

Cells need:

1) To Sense cues from their environment.
2) The ability to directionally Organize and Polarize their cytoskeleton.
3) To generate physical Force to move.
4) Persistence to keep "on-track"

Cell polarization, shape change and motility involves a coordinated
deployment in the cytoskeleton

• assembly and disassembly of polymers

• regulation and modification of their structure by proteins

• actions of motor proteins among the polyers

Yeast

• single cell eukaryote

• fungus with a chitin-cell wall

• uses both asexual and sexual reporduction

• Uses budding for cell proliferation of haploid and diploid

• a- and alpha-type haploids fuse by conjugation

• useful for protein function especially on humans

Yeast can polarize membranes in 2 ways

• Conjugation- polarized behavior during conjugation

• Budding- polarized assembly of new daughter cell during cell division

Neutrophils

immune cells that polarize to track invasive pathogens

Keratocytes

Are epidermal cells from fish/amphibian skin useful for studying cell motility due to being big and fast.

So large that they allow visualization of biochemistry within a cell

Chemotaxis

follow gradients of diffusible factors

Haptoaxis

track immobilized molecules

Durotaxis

follow gradients in substrate stiffness

Galvanotaxis

guided by applied voltage

Cell Motility II

• Polarity can occur at the Input layer.

  • intracellular (inside) signaling (outside)

• Core processes can be polarized

• Polarity must occur at the output layer

Universal Principles of Cell Motility:

• F-actin assembly and myosin contractility controlled by G-proteins.

• assembly of branched F-actin at the leading edge.

F-actin modifiers

capping protein, filamin (cross-linker), cofilin and formin (polymerization).

What do neurons do?

1) Dendrites - short - receive signals.
2) Axons - long - transmit signals

Lessons about cell polarity

Actin has cell cortex and allows extension by growth cone Microtubules are oriented assembly in axon to deliver vesicles to synapse Intermediate filaments hold the axon together into compact structure

Incredibly diverse connections start from same place but growth cones migrate to different locations

+ filopodia explore micro-environment.
+ cells bind and modify diverse signals
+ at target form finer structures such as synapses, bouttons, etc.
+ connect source and target cells

"Substrate" has different meanings in Metabolism and Cell Migration.

• In metabolism, a substrate is a chemical used in a reaction.
• In cell migration, a substrate is the surface used by the cell to adhere
and exert force

"Plus-end" and "minus-end" do not refer to electronic charge.

Neurons can have many growth cones. A single growth cone is to a neuron as a leading edge is to a migrating cell.

Permissive Factor

Factors that are a pre-requisite for any movement. Activates a cell prior to its polarization and movement

Instructive cue

Cues that are required for directional movements but not the movement itself. How does the environment guide cell movement? Instructive cues provide polarity within a cell that is already prepared for directed movements.

Duty Cycle of cell migration

0) BEFORE migrating, the cell must POLARIZE!
1) Directed polymerization
of F-actin.
2) Attachment of the leading
edge to the substratum.
3) Contractility at rear
pulls cell forward and rear
detaches. (Repeats_

Knock-out

Does not distinguish whether permissive or instructive

Widespead over expression

eliminates the possible gradient of an instruction

Perturb or relocate gradient of signaling "cue"

changes the direction of cell movements.

Calyculin A

drug that activates myosin II.

Gradient and levels of G-proteins RAC activity control cell velocity and persistence

1. Very low Rac Activity, migration inhibited

2. Lower Rac, high persistence, variable velocities (3D)

3. Higher Rac, high random, medium velocity (2D)

4. Highly activated RAC, migration inhibited

Optogenetic Control of RAC

Light-Oxygen-Voltage (LOV) sensing protein domain from plants. Jα - inhibitory protein module