|Cell Locomotion - The lamellipod
|Above: a model of a resting animal cell, which is rounded up, but sitting on a flat solid surface. When
detached and floating in liquid many cells, such as white blood cells or animal cells in culture, tend to round
up into tiny balls. When they attach to a solid surface, like the one above, they may spread extensively. This
cell shows signs that it may be beginning to spread, as its shape is flattened. It is also slightly elongated,
suggesting that it is polarising, or developing a definite front and back end. Cells may spread very flat, like
fried eggs or pancakes, without polarising - they are more or less symmetrical in all directions. They may do
this to stick better to the surface but with no intentions of moving anywhere. However, depending on the cell
type and its stimulus, the cell may decide to move about or locomote by amoeboid locomotion, rather like an
amoeba. If you follow the link to the amoeba page, then you will see a video of a large amoeba in action.
Amoebae are single-celled proto-animals and the ancestor of all animals may well have resembled an
Although animals are multicellular, unlike the single-celled amoeba, there are times when animal cells need
to move around inside the animal body. One way they do this is by crawling like an ameoba, changing
shape as they go, like a flowing drop of semi-liquid slime! They will put out one or more elongated
appendage at the front end, which pulls or pushes the cell forward. Such an appendage may be a
shape-changing extension of the cell, called a pseudopod (like the amoeba in the video). Like the amoeba,
the pseudopod may be rounded and blunt, like a finger, in which case it is called a lobopod. However, many
cells (including some amoebas) spread their pseudopod as wide and flat as they can, gripping the substrate
with a fan-shaped splat of slimy protoplasm. Such a flat and broad veil or sheet-like pseudopod is called a
lamellipod. The cell above has gone on to form a lamellipod in the diagrams below. In these images it is
crawling towards you!
Above: the lamellipod is forming as the cell, essentially a gelatinous blob covered in slime, pushes itself
forward, rippling as waves travel toward the front edge (leading edge) of the lamellipod, in the direction
toward you. A short tail juts out the back, usually slightly elevated above the substratum, this is called a
uropod and has sensory functions. The main sensors are spread along the leading edge. You cannot see
these sensors, since they are nanoscale (submicroscopic) protein complexes that sit inside the cell
membrane which covers the whole cell, including the lamellipod.
Above: the lamellipod has continued to spread as the cell gets under way. Its sensors can respond to chemicals
in its environment, telling it where to go. Animal cells can also respond to the texture of the surface and any
forces exerting tension upon it, and they can also respond to light.
Above and below: the lamellipod is fully deployed and the cell is motoring toward you. The extent to which the
lamellipod spreads will depend upon the cell type, the nature of the surface it is crawling over and the degree
to which the cell is activated. Sometimes the cells are almost all lamellipod and very little body or uropod, and
they advance like crescentic sheets, rippling as they go. They may change direction many times, and they can
even reabsorb the lamellipod and set off in a new direction by extending a new lamellipod somewhere else.
Animal cells are generally not as fast as amoebae at crawling about, partly because most animal cells are
only about 10 micrometres across (about one hundredth of a millimetre) and extending to two or three times
this when flattened, whereas some amoeba are large cells, ten times the diameter or more of a typical animal
cell. Amoebae may crawl about at around 5 micrometres per second, whereas animal cells crawl about at
around 10 micrometres a minute. Also, animal cells don't need to hunt down prey to survive, so they can
afford to be slower, and it is probably better that they move slower, since they need to analyse the signals in
their environment to make sure they go the right way and don't end up in the wrong part of the body - that is
they need to be better coordinated. Some animal cells crawl even slower, such as fibroblasts which crawl
about the scaffolding of the body's connective tissues (like skin, and tough sheets of supporting tissue within
the body) repairing and laying down new scaffolding (the scaffolding consists of minute criss-crossing
rope-like proteins like collagen, which is stronger than steel and more elastic fibres). Thus, fibroblasts don't
need to be fast, they just crawl around slowly, doing their work. White blood cells tend to be faster, since they
need to get to the sites of infection and gobble up bacteria quickly. Invasive cancer and tumour cells may
also move around fast. These are cells with damaged communications apparatus and they are unable to
receive proper instructions from the body, and so they revert to a more wild state and may roam around the
body, feeding and multiplying at will.
So, how do cells do this neat trick?
Animal cells (and also amoebae and plant cells - eukaryotic cells) possess an internal skeleton, called the
cytoskeleton. This skeleton is not made of bone (!) but from protein tubes and filaments that can join
together to form networks. These proteins support the cell, and also move it by changing its shape and
enabling it to crawl. These protein tubes have an odd property - the cell can dissolve or assemble them at
will, whenever and wherever they are needed. When the cell forms a lamellipod (lamellipodium) one of the
key proteins involved is actin. Actin can be dissolved into solution, or it can be assembled into networks of
tiny filaments or rods. In the lamellipod, these rods form a network in which they lie more or less
perpendicular to the leading edge of the cell, as they grow by lengthening only at the front end and so they
push the cell membrane outwards, extending the lamellipod.
This is shown in the diagram below, which also shows some of the detailed features often asociated with
lamellipods (and not shown in our 3D models, though the precise nature of the lamellipod varies with cell
Above: top - the front end of a migrating human cell, moving to the right (arrow). The lamellipod has
sensory spikes protruding from it, called microspikes, and membrane ruffles, where the lamellipod
advances in ripples. Bottom - a section of the lamellipod (indicated by the red circle) is shown, with the
direction of movement toward the top of the page (arrow). The striped lines are the filaments of actin
(called F-actin or filamentous actin) which form a mesh. These filaments push the cell mebrane forward
as they grow at their front ends. Shown here are G-actin (globular actin) monomers at the rear of the
mesh. These are the individual protein units that polymerise to form the F-actin and are water-soluble.
Here the lamellipod is dissolving at its rear and not advancing much, because the cell is heading in a
different direction - these F-actin meshes are dynamic, they form and dissolve as required, where and
when required! Complexes of proteins, called membrane binding complexes (MBCs, red circles) bind the
mesh to the membrane at intervals. The linker protein, alpha-actinin (black rods) bind adjacent actin
filaments together to form stronger bundles that push the cell forward as they extend by growing.
Also shown are Arp2/3 protein complexes which initiate the formation of new F-actin branches in the
mesh. Myosin proteins, which act like small engines carrying cargo along the actin filaments as though
they were rail-lines. (If the cell is on the move then it must keep all its bits moving with it!). Gelsolin (a
protein enzyme) helps to dissolve the actin mesh by cutting the filaments into smaller pieces. The mesh
will dissolve when it is no longer needed. It will also dissolve at the rear as it grows at the front, moving it
along with the cell it is driving. Cofilin (a member of the ADF protein family) also helps to dissolve or
depolymerise the mesh.
The cup-like receptors at the front of the cell are sensors. These may respond, for example, to chemical
signals, such as those released by damaged cells, and tell the cell where to go, e.g. to help repair the
damage. If the correct chemical binds to these sensors, they may trigger actin polymerise to such an
extent that the lamellipod starts growing again and the cell may set off in this new direction. In this way the
cell keeps on target and steers toward the source of the chemical signal.
To put things into perspective, each acting filament or rod is only 7 millionths of a millimetre (7
nanometres, 7 nm) in diameter! The real machinery is much more complex than shown here, and many
more proteins are involved (about 300 proteins that associate with actin, called actin-binding proteins
(ABP) are known, of which the few proteins shown here are key examples). All-in-all the cell has a
complicated 'lego' or 'mechano' kit from which it builds its motors and skeleton as needed, in a matter of
seconds, and then disassembles them when they are no longer needed!
The following is a brief description of some of the key ABPs:
1. Some ABPs that cross-link actin filaments into bundles and/or bind F-actin to the CM:
A-actinin: cross-links acting filaments to form bundles. Also links membrane-receptors to actin (as does
Talin: cross-links actin filaments into bundles and links actin to membrane receptors, such as integrins
(as does a-actinin).
Ponticulin: an integral membrane protein that binds F-actin.
Vinculin: links integrins to actin (in focal adhesion plaques). The protein a-catenin serves a similar
Fascin: spaced at 11 nm along actin bundles and cross-links them into an hexagonal array.
Fimbrin: cross-links actin into tight bundles in active processes, e.g. filopod formation.
Filamin: a crucial actin cross-linking protein in determining the 3D arrangement of actin filament networks.
Membrane-binding complexes: various complexes of proteins that bind actin to the cell membrane.
They may also bind the actin to cell surface receptors, perhaps in response to a ligand binding the
receptor. If the ligand is part of the extracellular matrix then the cell may form an adhesion junction with
2. Some ABPs that facilitate polymerisation of actin:
Profilin: binds to G-actin, facilitating its polymerisation.
Arp2/3 complex: a seven subunit protein complex. Serves as nucleation sites for new actin filaments.
Binds to an existing actin filament and initiates formation of a new daughter filament angled at 70 degrees
to the mother filament. Causing branching of actin network.
SCAR/WAVE: thought to activate Arp2/3, localised in lamellipod tip. A WASP (WASp) family protein.
Essential for lamellipod and filopod formation - SCAR/WAVE-Arp2/3 signaling pathway.
Cortactin: recruits Arp2/3 complex to existing actin filaments to initiate branching.
Ena/VASP: anti-capping proteins (antagonise capping proteins).
3. Some ABPs that facilitate depolymerisation of actin:
ADF Cofilin (cofilin): binds G-actin; depolymerises F-actin by severing filaments and by increasing the
actin monomer off-rate (at the pointed ends).
Gelsolin: severs actin filaments and caps actin filament barbed ends to prevent further polymerisation.
Thymosin: binds to G-actin, preventing its polymerisation.
Assembly and disassembly of a single actin filament:
Profilin, thymosin b4: actin monomer-binding proteins that maintain a pool of Mg-ATP-actin monomers
in the cell. Profilin bound actin monomers (but NOT that bound by thymosin) can polymerise.
Profilin-Mg-ATP-actin polymerises at the barbed end of the actin filament (AF).
Gelsolin: dissolves cross-linked actin gels (gel to sol transition) by severing actin filaments (increasing
the number of nucleation sites) and by capping barbed ends to prevent polymerisation (capping-protein,
The diagram below shows the actin assembly/disassembly cycle: click the thumbnail to enlarge