| Cell biology | |
|---|---|
| Animal cell diagram | |
 Components of a typical animal cell:
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Thecytosol, also known ascytoplasmic matrix orgroundplasm,[2] is one of the liquids found inside cells (intracellular fluid (ICF)).[3] It is separated into compartments by membranes. For example, themitochondrial matrix separates the mitochondrion into many compartments.
In theeukaryotic cell, the cytosol is surrounded by thecell membrane and is part of thecytoplasm, which also comprises the mitochondria,plastids, and otherorganelles (but not their internal fluids and structures); thecell nucleus is separate. The cytosol is thus a liquid matrix around the organelles. Inprokaryotes, most of the chemical reactions ofmetabolism take place in the cytosol, while a few take place in membranes or in theperiplasmic space. In eukaryotes, while manymetabolic pathways still occur in the cytosol, others take place within organelles.
The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and properties within cells is not well understood. The concentrations ofions such assodium andpotassium in the cytosol are different to those in theextracellular fluid; these differences in ion levels are important in processes such asosmoregulation,cell signaling, and the generation ofaction potentials in excitable cells such as endocrine, nerve and muscle cells. The cytosol also contains large amounts ofmacromolecules, which can alter how molecules behave, throughmacromolecular crowding.
Although it was once thought to be a simple solution of molecules, the cytosol has multiple levels of organization. These includeconcentration gradients of small molecules such ascalcium, large complexes ofenzymes that act together and take part inmetabolic pathways, andprotein complexes such asproteasomes andcarboxysomes that enclose and separate parts of the cytosol.
The term "cytosol" was first introduced in 1965 by H. A. Lardy, and initially referred to the liquid that was produced by breaking cells apart and pelleting all the insoluble components byultracentrifugation.[4][5] Such a soluble cell extract is not identical to the soluble part of the cell cytoplasm and is usually called a cytoplasmic fraction.[6]
The termcytosol is now used to refer to the liquid phase of the cytoplasm in an intact cell.[6] This excludes any part of the cytoplasm that is contained within organelles.[7] Due to the possibility of confusion between the use of the word "cytosol" to refer to both extracts of cells and the soluble part of the cytoplasm in intact cells, the phrase "aqueous cytoplasm" has been used to describe the liquid contents of the cytoplasm of living cells.[5]
Prior to this, other terms, includinghyaloplasm,[8] were used for the cell fluid, not always synonymously, as its nature was not well understood (seeprotoplasm).[6]
The proportion of cell volume that is cytosol varies: for example while this compartment forms the bulk of cell structure inbacteria,[9] in plant cells the main compartment is the large centralvacuole.[10] The cytosol consists mostly of water, dissolved ions, small molecules, and large water-soluble molecules (such as proteins). The majority of these non-protein molecules have amolecular mass of less than 300 Da.[11] This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (themetabolites) is immense. For example, up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell.[12] Estimates of the number of metabolites in single cells such asE. coli andbaker's yeast predict that under 1,000 are made.[13][14]
Most of the cytosol iswater, which makes up about 70% of the total volume of a typical cell.[15] ThepH of the intracellular fluid is 7.4.[16] while mouse cell cytosolicpH ranges between 7.0 and 7.4, and is usually higher if a cell is growing.[17] Theviscosity of cytoplasm is roughly the same as pure water, althoughdiffusion of small molecules through this liquid is about fourfold slower than in pure water, due mostly to collisions with the large numbers ofmacromolecules in the cytosol.[18] Studies in thebrine shrimp have examined how water affects cell functions; these saw that a 20% reduction in the amount of water in a cell inhibits metabolism, with metabolism decreasing progressively as the cell dries out and all metabolic activity halting when the water level reaches 70% below normal.[5]
Although water is vital for life, the structure of this water in the cytosol is not well understood, mostly because methods such asnuclear magnetic resonance spectroscopy only give information on the average structure of water, and cannot measure local variations at the microscopic scale. Even the structure of pure water is poorly understood, due to the ability of water to form structures such aswater clusters throughhydrogen bonds.[19]
The classic view of water in cells is that about 5% of this water is strongly bound in by solutes or macromolecules as water ofsolvation, while the majority has the same structure as pure water.[5] This water of solvation is not active inosmosis and may have different solvent properties, so that some dissolved molecules are excluded, while others become concentrated.[20][21] However, others argue that the effects of the high concentrations of macromolecules in cells extend throughout the cytosol and that water in cells behaves very differently from the water in dilute solutions.[22] These ideas include the proposal that cells contain zones of low and high-density water, which could have widespread effects on the structures and functions of the other parts of the cell.[19][23] However, the use of advanced nuclear magnetic resonance methods to directly measure the mobility of water in living cells contradicts this idea, as it suggests that 85% of cell water acts like that pure water, while the remainder is less mobile and probably bound to macromolecules.[24]
The concentrations of the otherions in cytosol are quite different from those inextracellular fluid and the cytosol also contains much higher amounts of charged macromolecules such as proteins and nucleic acids than the outside of the cell structure.
| Ion | Concentration (millimolar) | |
|---|---|---|
| In cytosol | In plasma | |
| Potassium | 139–150[25][26] | 4 |
| Sodium | 12 | 145 |
| Chloride | 4 | 116 |
| Bicarbonate | 12 | 29 |
| Amino acids in proteins | 138 | 9 |
| Magnesium | 0.8 | 1.5 |
| Calcium | <0.0002 | 1.8 |
In contrast to extracellular fluid, cytosol has a high concentration ofpotassium ions and a low concentration ofsodium ions.[27] This difference in ion concentrations is critical forosmoregulation, since if the ion levels were the same inside a cell as outside, water would enter constantly byosmosis - since the levels ofmacromolecules inside cells are higher than their levels outside. Instead, sodium ions are expelled and potassium ions taken up by theNa⁺/K⁺-ATPase, potassium ions then flow down their concentration gradient through potassium-selection ion channels, this loss of positive charge creates a negativemembrane potential. To balance thispotential difference, negative chloride ions also exit the cell, through selective chloride channels. The loss of sodium and chloride ions compensates for the osmotic effect of the higher concentration of organic molecules inside the cell.[27]
Cells can deal with even larger osmotic changes by accumulatingosmoprotectants such asbetaines ortrehalose in their cytosol.[27] Some of these molecules can allow cells to survive being completely dried out and allow an organism to enter a state of suspended animation calledcryptobiosis.[28] In this state the cytosol and osmoprotectants become a glass-like solid that helps stabilize proteins and cell membranes from the damaging effects of desiccation.[29]
The low concentration ofcalcium in the cytosol allows calcium ions to function as asecond messenger incalcium signaling. Here, a signal such as ahormone or anaction potential openscalcium channel so that calcium floods into the cytosol.[30] This sudden increase in cytosolic calcium activates other signalling molecules, such ascalmodulin andprotein kinase C.[31] Other ions such as chloride and potassium may also have signaling functions in the cytosol, but these are not well understood.[32]
Protein molecules that do not bind tocell membranes or thecytoskeleton are dissolved in the cytosol. The amount of protein in cells is extremely high, and approaches 200 mg/ml, occupying about 20–30% of the volume of the cytosol.[1] However, measuring precisely how much protein is dissolved in cytosol in intact cells is difficult, since some proteins appear to be weakly associated with membranes or organelles in whole cells and are released into solution uponcell lysis.[5] Indeed, in experiments where the plasma membrane of cells were carefully disrupted usingsaponin, without damaging the other cell membranes, only about one quarter of cell protein was released. These cells were also able to synthesize proteins if given ATP and amino acids, implying that many of the enzymes in cytosol are bound to the cytoskeleton.[33] However, the idea that the majority of the proteins in cells are tightly bound in a network called themicrotrabecular lattice is now seen as unlikely.[34]
In prokaryotes the cytosol contains the cell'sgenome, within a structure known as anucleoid.[35] This is an irregular mass ofDNA and associated proteins that control thetranscription andreplication of the bacterialchromosome andplasmids. In eukaryotes the genome is held within thecell nucleus, which is separated from the cytosol bynuclear pores that block the free diffusion of any molecule larger than about 10 nanometres in diameter.[36]
This high concentration of macromolecules in cytosol causes an effect calledmacromolecular crowding, which is when theeffective concentration of other macromolecules is increased, since they have less volume to move in. This crowding effect can produce large changes in both therates and the position ofchemical equilibrium of reactions in the cytosol.[1] It is particularly important in its ability to alterdissociation constants by favoring the association of macromolecules, such as when multiple proteins come together to formprotein complexes, or whenDNA-binding proteins bind to their targets in thegenome.[37]
Although the components of the cytosol are not separated into regions by cell membranes, these components do not always mix randomly and several levels of organization can localize specific molecules to defined sites within the cytosol.[38]
Although small moleculesdiffuse rapidly in the cytosol, concentration gradients can still be produced within this compartment. A well-studied example of these are the "calcium sparks" that are produced for a short period in the region around an opencalcium channel.[39] These are about 2 micrometres in diameter and last for only a fewmilliseconds, although several sparks can merge to form larger gradients, called "calcium waves".[40] Concentration gradients of other small molecules, such asoxygen andadenosine triphosphate may be produced in cells around clusters ofmitochondria, although these are less well understood.[41][42]
Proteins can associate to formprotein complexes, these often contain a set of proteins with similar functions, such as enzymes that carry out several steps in the same metabolic pathway.[43] This organization can allowsubstrate channeling, which is when the product of one enzyme is passed directly to the next enzyme in a pathway without being released into solution.[44] Channeling can make a pathway more rapid and efficient than it would be if the enzymes were randomly distributed in the cytosol, and can also prevent the release of unstable reaction intermediates.[45] Although a wide variety of metabolic pathways involve enzymes that are tightly bound to each other, others may involve more loosely associated complexes that are very difficult to study outside the cell.[46][47] Consequently, the importance of these complexes for metabolism in general remains unclear.
Some protein complexes contain a large central cavity that is isolated from the remainder of the cytosol. One example of such an enclosed compartment is theproteasome.[48] Here, a set of subunits form a hollow barrel containingproteases that degrade cytosolic proteins. Since these would be damaging if they mixed freely with the remainder of the cytosol, the barrel is capped by a set of regulatory proteins that recognize proteins with a signal directing them for degradation (aubiquitin tag) and feed them into the proteolytic cavity.[49]
Another large class of protein compartments arebacterial microcompartments, which are made of a protein shell that encapsulates various enzymes.[50] These compartments are typically about 100–200nanometres across and made of interlocking proteins.[51] A well-understood example is thecarboxysome, which contains enzymes involved incarbon fixation such asRuBisCO.[52]
Non-membrane bound organelles can form asbiomolecular condensates, which arise by clustering,oligomerisation, orpolymerisation ofmacromolecules to drivecolloidal phase separation of the cytoplasm or nucleus.
Although thecytoskeleton is not part of the cytosol, the presence of this network of filaments restricts the diffusion of large particles in the cell. For example, in several studies tracer particles larger than about 25 nanometres (about the size of aribosome)[53] were excluded from parts of the cytosol around the edges of the cell and next to the nucleus.[54][55] These "excluding compartments" may contain a much denser meshwork ofactin fibres than the remainder of the cytosol. These microdomains could influence the distribution of large structures such asribosomes and organelles within the cytosol by excluding them from some areas and concentrating them in others.[56]
The cytosol is the site of multiple cell processes. Examples of these processes includesignal transduction from the cell membrane to sites within the cell, such as thecell nucleus,[57] or organelles.[58] This compartment is also the site of many of the processes ofcytokinesis, after the breakdown of thenuclear membrane inmitosis.[59] Another major function of cytosol is to transport metabolites from their site of production to where they are used. This is relatively simple for water-soluble molecules, such as amino acids, which can diffuse rapidly through the cytosol.[18] However,hydrophobic molecules, such asfatty acids orsterols, can be transported through the cytosol by specific binding proteins, which shuttle these molecules between cell membranes.[60][61] Molecules taken into the cell byendocytosis or on their way to besecreted can also be transported through the cytosol insidevesicles,[62] which are small spheres of lipids that are moved along the cytoskeleton bymotor proteins.[63]
The cytosol is the site of most metabolism in prokaryotes,[9] and a large proportion of the metabolism of eukaryotes. For instance, in mammals about half of the proteins in the cell are localized to the cytosol.[64] The most complete data are available in yeast, where metabolic reconstructions indicate that the majority of both metabolic processes and metabolites occur in the cytosol.[65] Major metabolic pathways that occur in the cytosol in animals areprotein biosynthesis, thepentose phosphate pathway,glycolysis andgluconeogenesis.[66] The localization of pathways can be different in other organisms, for instance fatty acid synthesis occurs inchloroplasts in plants[67][68] and inapicoplasts inapicomplexa.[69]
