molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, treadmilling is a phenomenon observed within

protein filament In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, st ...

s of the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

s of many

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

s, especially in

actin filament Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pro ...

s and

microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

. 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 The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

. This is due to the constant removal of the

protein subunit In structural biology, a protein subunit is a polypeptide chain or single protein molecule that assembles (or "''coassembles''") with others to form a protein complex. Large assemblies of proteins such as viruses often use a small number of ty ...

s from these filaments at one end of the filament, while protein subunits are constantly added at the other end. Treadmilling was discovered by Wegner, who defined the

thermodynamic Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of ther ...

and

kinetic Kinetic (Ancient Greek: κίνησις “kinesis”, movement or to move) may refer to: * Kinetic theory of gases, Kinetic theory, describing a gas as particles in random motion * Kinetic energy, the energy of an object that it possesses due to i ...

constraints. Wegner recognized that: “The

equilibrium constant The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemical system after sufficient time has elapsed at which its composition has no measurable tendency ...

(K) for association of a

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

with a

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

is the same at both ends, since the addition of a monomer to each end leads to the same polymer.”; a simple reversible polymer can’t treadmill;

ATP hydrolysis ATP hydrolysis is the catabolic reaction process by which chemical energy that has been stored in the high-energy phosphoanhydride bonds in adenosine triphosphate (ATP) is released after splitting these bonds, for example in muscles, by prod ...

is required. GTP is hydrolyzed for microtubule treadmilling.

Detailed process

Dynamics of the filament

The

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

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s relies on directed growth of actin filaments at the cell front (''leading edge'').

Microfilaments

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. Elongating the actin filament occurs when free-actin (G-actin) bound to ATP associates with the filament. Under physiological conditions, it is easier for G-actin to associate at the positive end of the filament, and harder at the negative end. However, it is possible to elongate the filament at either end. Association of G-actin into F-actin is regulated by the critical concentration outlined below. Actin polymerization can further be regulated by

profilin Profilin is an actin-binding protein involved in the dynamic turnover and reconstruction of the actin cytoskeleton. It is found in all eukaryotic organisms. Profilin is important for spatially and temporally controlled growth of actin microfilame ...

and

cofilin ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle contractio ...

. Cofilin functions by binding to ADP-actin on the negative end of the filament, destabilizing it, and inducing depolymerization. Profilin induces ATP binding to G-actin so that it can be incorporated onto the positive end of the filament.

Microtubules

Two main theories exist on microtubule movement within the cell: dynamic instability and treadmilling. Dynamic instability occurs when the microtubule assembles and disassembles at one end only, while treadmilling occurs when one end polymerizes while the other end disassembles.

Critical concentration

The critical concentration is the concentration of either G-actin (actin) or the alpha,beta- tubulin complex (microtubules) at which the end will remain in an equilibrium state with no net growth or shrinkage. What determines whether the ends grow or shrink is entirely dependent on the cytosolic concentration of available monomer subunits in the surrounding area. Critical concentration differs from the positive (C_C⁺) and the negative end (C_C⁻), and under normal physiological conditions, the critical concentration is lower at the positive end than the negative end. Examples in how the cytosolic concentration relates to the critical concentration and polymerization are as follows: * A cytosolic concentration of subunits above both the C_C⁺ and C_C⁻ ends results in subunit addition at both ends * A cytosolic concentration of subunits below both the C_C⁺ and C_C⁻ ends results in subunit removal at both ends Note that the cytosolic concentration of the monomer subunit between the C_C⁺ and C_C⁻ ends is what is defined as treadmilling in which there is growth at the plus end, and shrinking on the minus end. The cell attempts to maintain a subunit concentration between the dissociation constants at the plus and minus ends of the polymer.

Microtubule treadmilling

Microtubules formed from pure tubulin undergo subunit uptake and loss at ends by both random exchange diffusion, and by a directional (treadmilling) element. Treadmilling is inefficient, and for microtubules at steady state: the Wegner s-value¹ (the reciprocal of the number of molecular events required for the net uptake of a subunit) is equal to 0.0005-0.001; i.e., it requires >1000 events. Microtubule treadmilling with pure tubulin also occurs with growing microtubules and is enhanced by proteins that bind to ends¹¹. Rapid treadmilling occurs in cells. FtsZ treadmilling The bacterial tubulin homolog FtsZ is one of the best documented treadmilling polymers. FtsZ assembles into protofilaments that are one subunit thick, which can further associate into small patches of parallel protofilaments. Single filaments and/or patches have been demonstrated to treadmill in vitro and inside bacterial cells. A Monte Carlo model of FtsZ treadmilling has been designed, based on a conformational change of subunits upon polymerization and GTP hydrolysis.

References

{{reflist

External links

Treadmill Finder
Cell movement Molecular biology