Often, in cellular Biology or Biomedical engineering, motility refers to directed cell movement down gradients established in biopolymers. Example are:
More information on cell motility can be found under Cell biology. Motility is also a term refering to the movement of stool through the intestines.
How do cells move?
All living things need some basic raw materials and energy for survival, and as the world is not generally kind enough to deliver these things right to the organism, many have evolved ways of bringing themselves to where they want to be. In this essay I will look into how individual cells propel themselves around the world, or even just get part of themselves there, which is often good enough.
The first method of movement I would like to discuss is the ability of some cells to crawl over their substrate by sending out extensions of their plasmalemma and cytoplasm called filopodia, anchoring themselves by said extension, then dragging themselves towards the anchor, or flowing into the filopodium. This mechanism of movement is famously used by amoeboid organisms, but is also used by lymphocytes, neutrophils and keratocytes to reach the sites of injury or infection to which they respond, and by cells in developing embryos to get where they ought to be, and to shape their substrate with their passage. To understand this mechanism of movement we must first examine the nature of the actin: Actin is a protein monomer that can assemble into filaments by attaching in a twisting manner so that each molecule of actin in a filament (bar the ones on the end) is bonded non-covalently with 4 other actin molecules; resulting in helictical fibres. This makes actin filaments much more stable then if the monomers only bonded with two other monomers. The advantage of actin filaments being composed of multiple monomers is that it allows the components of actin filaments (which may have to stretch the width of a cell) to diffuse around the cell and be available where required. Large structures can be assembled where required, then disassembled when no longer needed and diffused until they are again needed somewhere else. However, actin is also liable to disassociate from the filament, so dimers are relatively unstable. However, a trimer of actin is much more stable, as there are more contacts between adjacent monomers. Thus, in vitro, actin in solution displays a lag time before it starts assembling into microfilaments, as it takes a while for the chance occurrence of enough additions to form a nucleus. Addition of pre-made nuclei removes this lag phase. The number of monomers that add to the actin filament (or microtubule, for that matter) is proportional to the concentration of free subunits in the solution. However, subunits will leave the polymer at a constant rate independent of the rate of addition. Thus, as free subunits are used up from the surrounding to make polymers, the rate of addition will drop until it reaches the critical concentration: the concentration at which addition and loss are equal. The polymer is not stable: it is constantly losing subunits (usually from one end, called the minus end, which due to the structure of actin has a lower affinity for other actin monomers) and gaining units (from the plus end, which has a higher affinity for actin monomers); this effect is known as treadmilling. Cells can control the formation of microfilaments by making nuclei available to skip the lag phase. These nuclei take the form of actin related proteins (ARPs), which are 45% similar to actin; ARP complexes composed of ARP2 and ARP3 and other proteins act as nuclei for the minus end of actin filaments, stabilising the minus end thus promoting elongation at the plus end. However, this only promotes filament growth: if this were the only control mechanism other random filaments would occur in the cell as in solution actin in vitro the critical concentration of actin is 1 μM, and the rest would turn eventually into microfilaments. In the cytosol actin is divided about 50/50 between free monomers and filaments. This reduction in how much actin is polymerised is achieved by special proteins, the most common of which is thymosin. Thymosin binds to actin monomers preventing them from binding to other actin monomers. Thus normally actin is prevented from forming polymers. Another protein, profilin, competes with thymosin, and when profilin binds to an actin monomer the resultant actin-profilin complex can attach to the plus end of microfilament (or filament nucleus), but not the minus end. The binding of the actin-profilin complex causes a conformational change in the actin, reducing its affinity for profilin, and the profilin disassociates. Now we can start to see how this is used as a means of movement: profilin is localised on the cytosolic face of the plasmalemma because it binds to acidic phospholipids that are found there. Thus the actin pushes out, forming extensions in the membrane – our filopodia or lemellipodia, by a process called protrusion. Protrusion can come in the form of filopodia (a spike of actin pushing out making a long, thing and narrow protrusion), lamellipodia (sheet like structures that are long, thing and wide) and pseudopodia (stubby three dimensional protrusions filled with actin gel). Now all we need is an anchor and a mechanism for pulling on the anchor. The anchor comes in the form of Focal Contacts. Focal Contacts are points produced on the newly protruded protrusion containing integrins where the plasma membrane is very close to the substrate. The actin filaments are connected to the intergrins that connect to the substrate, and attachment is achieved. Now the actin filaments, which are usually attached to each other by ARP complexes forming a web, which undergoes treadmilling: assembling at the front and disassembling at the back. Cofilin is used to control unidirectional movement as it will bind preferentially and cause depolymerisation to actin that contains ADP, thus the later parts of the web are targeted over the newly polymerised parts. Actin acts as an enzyme, and while ATP hydrolysis rates are very low in the monomer form, in the polymer form hydrolysis of ATP to ADP is much higher. Thus traction is achieved by treadmilling. The mechanism by which the contents of the cell move forward is not fully understood, but it is known that these forces are generated by myosin II. Contraction of the actin cortex at the posterior end helps weaken older focal points. And thus, the cell crawls forward.
The next method of cell motility I would like to discuss is the eukaryotic flagella and cilia. These, like filopodia, are extensions of the cytoplasm, but in this case they are caused by the protrusion of tubulin. Tubulin is a protein that can assemble into microtubules by the polymerisation of many tubulin dimers. Tubulin dimers are composed of two separate proteins: α-tubulin and β-tubulin. These dimers assemble head to tail to form protofilaments. 12 protofilaments line up side by side and curve around to form a hollow tube – this is a microtubule. Cilia and flagella have a core (called an axoneme) of 9 outer doublet microtubules, which consist of a full microtubule and a partial microtubule fused together, with a pair of full microtubules in the centre. The outer doublet microtubules are connected to the inner singlet tubules by radial spokes, and are connected to their neighbouring doublet tubules by nexin. The doublet microtubules are also attached to each other by dynein. This molecule has a motor domain that when activated by ATP hydrolysis ‘walks’ along the adjacent doublet microtubule by a mechanism similar to myosin in muscle cells. This would make the microtubules slide past each other if it was not for the connective nexin. As they are connected by nexin, a bending motion occurs, thus making the cilia or flagella wave back and forth. This can propel the cell forward in a liquid medium: either one or a few large flagella are used (as in sperm cells) or banks of shorter cilia beating slightly out of synchrony to produce a waving effect.
Eukaryotic flagella however are totally different to prokaryotic flagella; a prokaryotic flagellum is a helically shaped filament of the protein flagellin attached to a base called a Hook, as it is bent at a significant angle. This hook is spun clockwise or anticlockwise by Mot complexes – the direction being controlled by Fli proteins. The Mot complexes are powered by an H+ gradient set up by actively pumping H+ out of the cytoplasm. The collective term for the Mot protein, Fli protein and various anchorage rings complex is the basal body. Flagella are arranged differently on different bacteria – either at one or both ends of a cell (known as polar flagellation) or all around the cell in peritrichous flagellation. The spinning of the semi-rigid flagellin filament acts as a screw or a drill to push or pull through the liquid substrate. In polar flagellation clockwise rotation of a flagellum on the left side of a bacterium pulls the bacterium left, and counter clockwise pushes it right. In peritrichous flagellation counter clockwise spinning causes the flagella to wrap around themselves in a bundle to one side and act as a large screw, pushing the bacterium forward. Clockwise rotation causes the bundle to unfurl and the bacteria to rotate randomly (called tumbling). Thus a series of runs and tumbles ensues and the bacterium can move towards or away from a gradient by increasing or decreasing the length of runs. for example in the case of a chemical gradient If the chemical is an attractant runs where the change in chemical level lowers will be short, while runs with a rising chemical gradient will be long.
A related method of movement found only in spirochetes are axial filaments: these are composed of between two to more the 100 endoflagella that come out of both ends of the bacteria between the cell membrane and the cell wall. It is thought that rotation of the endoflagella in the perisplasmic space causes the corkscrew shaped outer membrane of the spirochete to rotate, moving the spirochete along.
Planktonic bacteria don’t necessarily have to swim to move to different areas of water. Cyanobacteria, for example, use gas vesicles to alter their buoyancy. This enables them to control their depth and so the amount of light they receive. Gas vesicles are spindle shaped hollow structures constructed of protein. The vesicle membrane is about 2nm thick and impermeable to water and solutes but permeable to most gasses. The gas vesicle is formed from two proteins, GvpA, which is arranged in a β sheet formation and makes up 97% of the vesicle. The other 3% is made up of GvpC ribs that strengthen the vesicle.
The cytosol of a cell is very viscous for an organism the size of a bacterium, so bacteria that replicate inside the cytosol (as opposed to in separate vesicles) and that must reach a certain position in the cell sequester the actin in the cell for their own use. Bacteria like Listeria monocytogenes stimulate the nucleation of actin monomers behind them, propelling them forward. This leaves a ‘comets tail’ of polymerised actin that depolymerises after about a minute. When a bacterium runs into the plasmallemma it keeps going for a bit, causing a thin extension of the plasma membrane, before bouncing back. Neighbouring cells are liable to engulf the extension, allowing the bacterium to invade the cell without exposing itself to antibodies in the extracellular environment. The mechanism for actin sequestering is not the same in every case, but in the case of L.monocytogenes proteins on the bacterial coat activate ARP complexes which cause the polymerisation.
Cells don’t necessarily have to move all of themselves to get where they are going: fungi, for example, just extend hyphae towards the nutrients they are in search of. Hyphae grow from the tip, from bodies known as spitzenkorper, or apical bodies. Positive internal pressure is maintained inside the hypha by active transport of small molecules into the cell to reduce the internal water potential. The tip of the hypha is more plastic then the side walls as lytic vesicle constantly fuse with the cell membrane, softening the chitin wall. Thus the water pressure pushes and stretches out the tip of the hypha. Chitisomes – vesicles containing inactivated chitinase zymogens – also fuse with the plasma membrane, releasing their content. Each chitisome produces a chitin fibre, and the myriad (over 40,000 a minute) of vesicles fusing at the tip keeps building the cell wall as the apical point is extended by hydrostatic pressure.
Being able to move from place to place is a highly adaptive trait, and so it is not surprising that all these motility mechanisms, and many more, have evolved to get cells where they are going.