WHAT ARE CILIA AND FLAGELLA?

Cilia and flagella are whip-like appendages of many living cells that are used to move fluid or to propel the cells. Cilia beat with an oar-like motion and flagella have a snake-like motion as illustrated in Figure 1. The cilia in your lungs keep dirt and dust from clogging your breathing tubes (the bronchi) by moving a layer of sticky mucous along to clean out the airways. Sperm cells use a flagellum as a propeller to move the cell through the fluid of the oviduct to reach the egg. Thousands of animals and plants use cilia and flagella for swimming (example: paramecium), or feeding (example: clams and mussels) or mating (example: green algae). It is a curious fact that all of these cilia and flagella have a very similar internal arrangement of tubes (the outer doublets) and protein connectors (the nexin links and dynein arms) that suggest that there is something very special about this particular way of building a cell propeller. Figure 2 is a diagram of these internal parts of a cilium. Nature tends to keep designs that work well. Possibly if we can understand why this particular design works so well we might be able to design miniature devices that use the same principles of operation!

beat patterns.jpg
beat patterns.jpg

Figure 1

Axoneme
Axoneme

Figure 2
external image bull%20axoneme%20photo.jpg external image mouse-axoneme-numbered.gif
An electron-microscopy image of a numbered bull axoneme and mouse axoneme, respectively.


THE GEOMETRIC CLUTCH MODEL
The Geometric Clutch model of ciliary and flagellar beating is a hypothesis that attempts to explain the way that cilia and flagella work. A computer model based on this hypothesis can do a fairly believable imitation of a cilium or a flagellum. The basic underlying idea of the Geometric Clutch hypothesis is rather simple to understand. When the molecular motors (dynein arms in the picture) that power the beat of the cilium or flagellum are activated they pull and push on the outer doublets and induce a strain on the structure that causes the cilium to bend. This part of the story of how cilia beat is agreed upon by all of the scientists that study cilia and flagella. The Geometric Clutch idea is that when the motors push and pull on the outer doublets the strain on each doublet creates a sideways force that is transverse to the doublet. This transverse force (or t-force) pushes some of the doublets closer together and others are pushed apart. The motors on the doublets that are pushed closer together go into action and generate force; the motors on doublets that are pulled apart are forced to stop pulling. In the Geometric Clutch model this is the working principle. The t-force controls the motors and acts like a "clutch", much as the clutch that engages or disengages the motor of your car. When this working principle is built into a computer simulation of a cilium or flagellum the simulated flagellum can produce repetitive beats that look very much like those of a real cilium or flagellum. A working copy of the Geometric Clutch computer simulation can be downloaded from the clutch model page of this web-site (http://www2.oakland.edu/biology/lindemann/clutch.htm). If you follow the instructions that are built in to the demonstration version you can make the model simulate a beating 10-micron long cilium (provided you are working from an IBM compatible PC).
These whiplike appendages extend from the surface of many types of eukaryotic cells.
  • If there are many of them, they are called cilia;
  • if only one, or a few, they are flagella. Flagella also tend to be longer than cilia but are otherwise similar in construction.

Cilia and flagella move liquid past the surface of the cell.
  • For single cells, such as sperm, this enables them to swim.
  • For cells anchored in a tissue, like the epithelial cells lining our air passages, this moves liquid over the surface of the cell (e.g., driving particle-laden mucus toward the throat).
Both cilia and flagella consist of:
  • a cylindrical array of 9 filaments consisting of: external image Satir.gif
    • a complete microtubule extending into the tip of the cilium;
    • a partial microtubule that doesn't extend as far into the tip.
    • cross-bridges of the motor protein dynein that extend from the complete microtubule of one filament to the partial microtubule of the adjacent filament.
  • a pair of single microtubules running up through the center of the bundle, producing the "9+2" arrangement.
  • The entire assembly is sheathed in a membrane that is an extension of the plasma membrane.
This electron micrograph (courtesy of Peter Satir) shows a cilium in cross section.
Each cilium (and flagellum) grows out from, and remains attached to, a basal body embedded in the cytoplasm. Basal bodies are identical to centrioles and are, in fact, produced by them. For example, one of the centrioles in developing sperm cells — after it has completed its role in the distribution of chromosomes during meiosis — becomes a basal body and produces the flagellum. The bending of cilia (and flagella) has many parallels to the contraction of skeletal muscle fibers.
In the case of cilia and flagella, dynein powers the sliding of the microtubules against one another — first on one side, then on the other.
  • Remember: the partial microtubules do not extend as far into the tip as the complete microtubules. external image Cilium.gif
  • So if a slice is made a short distance back from the tip,
    • A straight cilium should show the complete pattern (center of diagram).
    • In a bent cilium, approximately half the filaments on the upper side should be retracted because of the greater arc on the convex side. So the partial microtubules would disappear being drawn below the plane of the slice. As seen here, bending to the left causes the partial microtubules 4, 5, 6, 7, and 8 to disappear.
    • When the cilium bends the other way, the partial microtubules on the opposite side disappear while they reappear on what is now the lower or concave side.
  • Electron micrographs (made by Peter Satir) have verified this model precisely.

There are other parallels between the sliding filaments of skeletal muscle and the sliding microtubules of cilia.
  • Both are powered by ATP.
  • Dynein (like myosin) is the ATPase.
  • Both are regulated by calcium ions.

Motile, "9+2", cilia are found only on certain cells in the vertebrate body, e.g., the epithelia lining the airways.
But almost every cell in vertebrates has — or had — a single primary cilium. The primary cilium grows out of the older of the two centrioles that the cell inherited following mitosis.
The primary cilium does not beat because it lacks the central pair of microtubules; that is, it is "9+0".
Where functions have been identified, they all involve sensory reception.
Some examples:

A primary cilium extends from the apical surface of the epithelial cells lining the kidney tubules and monitors the flow of fluid through the tubules. Inherited defects in the formation of these cilia cause polycystic kidney disease.

We detect odors by receptors on the primary cilium of olfactory neurons.
During embryonic development (and probably later as well), many cells detect extracellular signaling molecules with receptors localized on their primary cilium. These signals are transduced into the nucleus where they alter gene expression.

The outer segment of the rods in the vertebrate retina is also derived from a primary cilium.
external image sea_urchin_sperm_axoneme.jpg

Cilia and flagella are made up of microtubules, which are composed of linear polymers of globular proteins called tubulin. The core (axoneme) contains two central fibers that are surrounded by an outer ring of nine double fibers and covered by the cellular membrane.

Ultrastructure of cilia and flagella
Ultrastructure of cilia and flagella


MOVEMENT OF CILIA AND FLAGELLA



These motile appendages are constructed by basal bodies (kinetostomes), which also function as centrioles. The basal body is located at the base of each filament, anchoring it to the cell and controlling its movement. Cilia and flagella have the same structure. The only difference is that the flagella are longer.
For single-celled eukaryotes, cilia and flagella are essential for the locomotion of individual organisms. Protozoans belonging to the phylum Ciliophora are covered with cilia. Flagella are a characteristic of the protozoan group Mastigophora.
In multicellular organisms, cilia function to move fluid or materials past an immobile cell as well as moving a cell or group of cells. The respiratory tract in humans is lined with cilia that keep inhaled dust, smog, and potentially harmful microorganisms from entering the lungs. Cilia generate water currents to carry food and oxygen past the gills of clams and transport food through the digestive systems of snails. Flagella are found primarily on gametes, but also create the water currents necessary for respiration and circulation in sponges and coelenterates.



Cilia and Flagella

Cilia and flagella are motile cellular appendages found in most microorganisms and animals, but not in higher plants. In multicellular organisms, cilia function to move a cell or group of cells or to help transport fluid or materials past them. The respiratory tract in humans is lined with cilia that keep inhaled dust, smog, and potentially harmful microorganisms from entering the lungs. Among other tasks, cilia also generate water currents to carry food and oxygen past the gills of clams and transport food through the digestive systems of snails. Flagella are found primarily on gametes, but create the water currents necessary for respiration and circulation in sponges and coelenterates as well. For single-celled eukaryotes, cilia and flagella are essential for the locomotion of individual organisms. Protozoans belonging to the phylum Ciliophora are covered with cilia, while flagella are a characteristic of the protozoan group Mastigophora.
In eukaryotic cells, cilia and flagella contain the motor protein dynein and microtubules, which are composed of linear polymers of globular proteins called tubulin. The core of each of the structures is termed the axoneme and contains two central microtubules that are surrounded by an outer ring of nine doublet microtubules. One full microtubule and one partial microtubule, the latter of which shares a tubule wall with the other microtubule, comprise each doublet microtubule (see Figure 1). Dynein molecules are located around the circumference of the axoneme at regular intervals along its length where they bridge the gaps between adjacent microtubule doublets.

external image 505px-Eukaryotic_cilium_diagram_en.svg.png


MOVEMENT OF FLAGELLA AND CILIA
Flagelle and cilia are structures that aid in locomotion and help move fluids across the surface of tissue cells in animals. Both flagella and cilia have a specialized arrangement of microtubules that is responsible for their locomotive ability. Cilia and flagella have an identical 9+2 microtubule arrangement. Nine pairs of fused microtubules surrounding an unfused pair of microtubules in the center. Using ATP as an energy source. The dynein arms of one microtuble grip the adjacent pair, pull, release, and then bind again. The microtubules can't slide past each other because they are anchored. The action of the dynein arms, then causes the microtubules to bend.

These whiplike appendages extend from the surface of many types of eukaryotic cells.
  • If there are many of them, they are called cilia;
  • if only one, or a few, they are flagella. Flagella also tend to be longer than cilia but are otherwise similar in construction.

Cilia and flagella move liquid past the surface of the cell.
  • For single cells, such as sperm, this enables them to swim.
  • For cells anchored in a tissue, like the epithelial cells lining our air passages, this moves liquid over the surface of the cell (e.g., driving particle-laden mucus toward the throat).

Both cilia and flagella consist of:
  • a cylindrical array of 9 filaments consisting of: external image Satir.gif
    • a complete microtubule extending into the tip of the cilium;
    • a partial microtubule that doesn't extend as far into the tip.
    • cross-bridges of the motor protein dynein that extend from the complete microtubule of one filament to the partial microtubule of the adjacent filament.
  • a pair of single microtubules running up through the center of the bundle, producing the "9+2" arrangement.
  • The entire assembly is sheathed in a membrane that is an extension of the plasma membrane.
This electron micrograph (courtesy of Peter Satir) shows a cilium in cross section.
Each cilium (and flagellum) grows out from, and remains attached to, a basal body embedded in the cytoplasm. Basal bodies are identical to centrioles and are, in fact, produced by them. For example, one of the centrioles in developing sperm cells — after it has completed its role in the distribution of chromosomes during meiosis — becomes a basal body and produces the flagellum.



external image Image119.gif
Cilia and Flagellas are commonly known as protrusions from some cells that aid in cellular locomotion.
They are formed from specialized groupings of microtubules called basal bodies.

Characteristics: Cilia and flagella have a core composed of microtubules connected to the plasma membrane arranged in what is known as a 9 + 2 pattern.
The pattern is so named because a ring of nine microtubule "doubles" has in its center two singular microtubules.
This organization allows the sliding of the microtubule doubles against one another to "bend" the cilia or flagella. This type of organization is found in most eukaryotic cilia and flagella.

Where can they be located?
Both cilia and flagella are found in numerous types of cells. For instance, the sperm of many animals, algae, and even ferns have flagella.
Cilia can be found in areas such as the respiratory and female reproductive tracts.

Movement:
Swimming is the major form of movement exhibited by sperm and by many protozoans. Some cells are propelled at velocities approaching 1 mm/s by the beating of cilia and flagella, flexible membrane extensions of the cell. Cilia and flagella range in length from a few microns to more than 2 mm in the case of some insect sperm flagella.




Eukaryotic cilia and flagella are generally differentiated based on size and number: cilia are usually shorter and occur together in much greater numbers than flagella, which are often solitary. The structures also exhibit somewhat different types of motion, though in both cases movement is generated by the activation of dynein and the resultant bending of the axoneme. The movement of cilia is often described as whip-like, or compared to the breast stroke in swimming. Adjacent cilia move almost simultaneously (but not quite), so that in groups of cilia, wave-like patterns of motion occur. Flagella, however, exhibit a smooth, independent undulatory type of movement in eukaryotes. Prokaryotic flagella, which have a completely different structure built from the protein flagellin, move in a rotating fashion powered by the basal motor.
Defects in the cilia and flagella of human cells are associated with some notable medical problems. For example, a hereditary condition known as Kartagener's syndrome is caused by problems with the dynein arms that extend between the microtubules present in the axoneme, and is characterized by recurrent respiratory infections related to the inability of cilia in the respiratory tract to clear away bacteria or other materials. The disease also results in male sterility due to the inability of sperm cells to propel themselves via flagella. Damage to respiratory cilia may also be acquired rather than inherited and is most commonly linked to smoking cigarettes. Bronchitis, for instance, is often triggered by a build-up of mucus and tar in the lungs that cannot be properly removed due to smoking-related impairment of cilia.