Treadmilling is a phenomenon observed in many cellular cytoskeletal filaments, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks resulting in a section of filament seemingly "moving" across a stratum or the cytosol. This is due to the constant removal of the protein subunits from these filaments at one end of the filament while protein subunits are constantly added at the other end.
Dynamics of the filament
The cytoskeleton is a highly dynamic part of a cell and cytoskeletal filaments constantly grow and shrink through addition and removal of subunits. Directed crawling motion of cells such as macrophages relies on directed growth of actin filaments at the cell front (leading edge).
The two ends of an actin filament differ in their dynamics of subunit addition and removal. They are thus referred to as the plus end (with faster dynamics, also called barbed end) and the minus end (with slower dynamics, also called pointed end). This difference results from the fact that subunit addition at the minus end requires a conformational change of the subunits. Note that each subunit is structurally polar and has to attach to the filament in a particular orientation. As a consequence, the actin filaments are also structurally polar.
Polymerization dynamics are not only faster at the plus end, but in addition, the critical concentration is higher at the minus end than at the plus end. The critical concentration (CC) characterizes the concentration of free monomer subunits at which net filament growth equals net shrinkage. This peculiar property is crucial for the phenomenon of treadmilling (see below). According to the thermodynamic law of microscopic reversibility, the equilibrium constants should be equal at both filament ends in an equilibrium system (such as a dead cell deprived of the chemical fuel ATP). In a living cell, however, a non-equilibrium steady-state is maintained and ATP is constantly consumed (hydrolyzed) to power the addition of new subunits.
The situation for microtubules is similar, except GTP is hydrolyzed rather than ATP.
What determines whether the ends grow or shrink is entirely dependent on the cytosolic concentration of available monomer subunits in the surrounding area. Both the plus and the minus ends have a different critical concentration (CC). Examples in which the cytosolic concentration can affect the critical concentrations are as followed:
- A cytosolic concentration of subunits above both the CC+ and CC− ends results in subunit addition at both ends
- A cytosolic concentration of subunits below both the CC+ and CC− ends results in subunit removal at both ends
Both the plus and minus ends have different CC values and generally, the plus end will always have a lower CC value than the minus end. This is due to the increased ease of subunit addition to the plus end, leading to faster growth.
Note that the cytosolic concentration of the monomer subunit between the CC+ and CC− ends is what is defined as treadmilling in which there is growth at the plus end, and shrinking on the minus end.
While treadmilling may occur at different speeds at both ends, there is a concentration at which the speed of growth at the (+) end is equal to the rate of shrinkage at the (-) end. This is deemed steady-state treadmilling in which the net length of the treadmilling filament remains unchanged.
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