Editing Cell growth

{{short description|Increase of the total mass of the cancer cells}}
[[File:Cell proliferation.jpg|thumb|Cell division, growth & proliferation]]
{{TopicTOC-Biology}}
'''Cell growth''' refers to an increase in the total [[mass]] of a [[cell (biology)|cell]], including both [[cytoplasm]]ic, [[cell nucleus|nuclear]] and [[organelle]] volume.<ref name="ConlonRaff1999">{{cite journal|last1=Conlon|first1=Ian|last2=Raff|first2=Martin|title=Size Control in Animal Development|journal=Cell|volume=96|issue=2|year=1999|pages=235–244|issn=0092-8674|doi=10.1016/S0092-8674(00)80563-2|pmid=9988218|s2cid=15738174|doi-access=free}}</ref> Cell growth occurs when the overall rate of cellular [[biosynthesis]] (production of [[biomolecules]] or anabolism) is greater than the overall rate of cellular degradation (the destruction of [[biomolecules]] via the [[proteasome]], [[lysosome]] or [[autophagy]], or catabolism).<ref name="GrewalEdgar2003">{{cite journal|last1=Grewal|first1=Savraj S|last2=Edgar|first2=Bruce A|journal=Journal of Biology|title=Controlling cell division in yeast and animals: does size matter?|volume=2|issue=1|year=2003|pages=5|issn=1475-4924|doi=10.1186/1475-4924-2-5|pmid=12733996|pmc=156596|doi-access=free}}</ref><ref name="Neufeldde la Cruz1998">{{cite journal|last1=Neufeld|first1=Thomas P|last2=de la Cruz|first2=Aida Flor A|last3=Johnston|first3=Laura A|last4=Edgar|first4=Bruce A|title=Coordination of Growth and Cell Division in the Drosophila Wing|journal=Cell|volume=93|issue=7|year=1998|pages=1183–1193|issn=0092-8674|doi=10.1016/S0092-8674(00)81462-2|pmid=9657151|s2cid=14608744|doi-access=free}}</ref><ref name="Thompson">{{cite journal|last1=Thompson|first1=Barry J.|author-link=Barry James Thompson|year=2010|title=Developmental control of cell growth and division in Drosophila|journal=Current Opinion in Cell Biology|volume=22|issue=6|pages=788–794|doi=10.1016/j.ceb.2010.08.018|pmid=20833011}}</ref>

Cell growth is not to be confused with [[cell division]] or the [[cell cycle]], which are distinct processes that can occur alongside cell growth during the process of [[cell proliferation]], where a cell, known as the mother cell, grows and divides to produce two [[daughter cell]]s.<ref name="ConlonRaff1999"/> Importantly, cell growth and [[cell division]] can also occur independently of one another. During early [[embryonic development]] ([[cleavage (embryo)|cleavage]] of the [[zygote]] to form a [[morula]] and [[blastoderm]]), [[cell divisions]] occur repeatedly without cell growth. Conversely, some cells can grow without [[cell division]] or without any progression of the [[cell cycle]], such as growth of [[neurons]] during [[axon]]al pathfinding in [[nervous system]] development.

[[File:The Biological bulletin (20189537288).jpg|thumb|Cell division without cell growth during embryonic cleavage]]

In [[multicellular]] organisms, [[tissue growth]] rarely occurs solely through cell growth without [[cell division]], but most often occurs through [[cell proliferation]].<ref name="ConlonRaff1999"/> This is because a single cell with only one copy of the [[genome]] in the [[cell nucleus]] can perform [[biosynthesis]] and thus undergo cell growth at only half the rate of two cells. Hence, two cells grow (accumulate mass) at twice the rate of a single cell, and four cells grow at 4-times the rate of a single cell. This principle leads to an [[exponential growth|exponential]] increase of [[tissue growth]] rate (mass accumulation) during cell proliferation, owing to the [[exponential growth|exponential]] increase in cell number.

Cell size depends on both cell growth and [[cell division]], with a disproportionate increase in the rate of cell growth leading to production of larger cells and a disproportionate increase in the rate of cell division leading to production of many smaller cells. [[Cell proliferation]] typically involves balanced cell growth and [[cell division]] rates that maintain a roughly constant cell size in the exponentially proliferating population of cells.

Some special cells can grow to very large sizes via an unusual [[Endoreduplication|endoreplication]] cell cycle in which the [[genome]] is replicated during [[S-phase]] but there is no subsequent mitosis ([[M-phase]]) or cell division ([[cytokinesis]]). These large [[Endoreduplication|endoreplicating]] cells have many copies of the [[genome]], so are highly [[polyploid]].

[[Oocyte]]s can be unusually large cells in species for which embryonic development takes place away from the mother's body within an egg that is laid externally. The large size of some eggs can be achieved either by pumping in cytosolic components from adjacent cells through cytoplasmic bridges named ring canals (''[[Drosophila]]'') or by internalisation of nutrient storage granules (yolk granules) by [[endocytosis]] ([[frog]]s).

== Mechanisms of cell growth control ==

[[Cell biology|Cells]] can grow by increasing the overall rate of cellular [[biosynthesis]] such that production of [[biomolecules]] exceeds the overall rate of cellular degradation of [[biomolecules]] via the [[proteasome]], [[lysosome]] or [[autophagy]].

[[Biosynthesis]] of [[biomolecules]] is initiated by expression of [[genes]] which encode [[RNA]]s and/or [[proteins]], including [[enzymes]] that catalyse synthesis of [[lipids]] and [[carbohydrates]].

Individual [[genes]] are generally [[regulation of gene expression|expressed]] via [[transcription (biology)|transcription]] into [[messenger RNA]] (mRNA) and [[translation (biology)|translation]] into [[protein]]s, and the expression of each gene occurs to various different levels in a cell-type specific fashion (in response to [[gene regulatory networks]]).

To drive cell growth, the global rate of gene expression can be increased by enhancing the overall rate of [[transcription (biology)|transcription]] by [[RNA polymerase II]] (for active genes) or the overall rate of [[messenger RNA|mRNA]] [[translation (biology)|translation]] into [[protein]] by increasing the abundance of [[ribosome]]s and [[tRNA]], whose [[ribosome biogenesis|biogenesis]] depends on [[RNA polymerase I]] and [[RNA polymerase III]]. The [[Myc]] [[transcription factor]] is an example of a regulatory protein that can induce the overall activity of [[RNA polymerase I]], [[RNA polymerase II]] and [[RNA polymerase III]] to drive global [[transcription (biology)|transcription]] and [[translation (biology)|translation]] and thereby cell growth.

In addition, the activity of individual [[ribosome]]s can be increased to boost the global efficiency of [[messenger RNA|mRNA]] [[translation (biology)|translation]] via regulation of translation initiation factors, including the 'translational elongation initiation factor 4E' ([[eIF4E]]) complex, which binds to and caps the 5' end of [[messenger RNA|mRNA]]s. The protein [[mTOR|TOR]], part of the [[mTORC1|TORC1]] complex, is an important upstream regulator of [[translation (biology)|translation]] initiation as well as [[ribosome biogenesis]].<ref name="Hafen2004">{{cite book|last1=Hafen|first1=E.|title=TOR|chapter=Interplay Between Growth Factor and Nutrient Signaling: Lessons from Drosophila TOR|series=Current Topics in Microbiology and Immunology|volume=279|year=2004|pages=153–167|issn=0070-217X|doi=10.1007/978-3-642-18930-2_10|pmid=14560957|isbn=978-3-642-62360-8}}</ref> [[mTOR|TOR]] is a serine/threonine [[kinase]] that can directly phosphorylate and inactivate a general inhibitor of [[eIF4E]], named [[EIF4EBP1|4E-binding protein (4E-BP)]], to promote translation efficiency. [[mTOR|TOR]] also directly phosphorylates and activates the ribosomal protein S6-kinase ([[S6K]]), which promotes [[ribosome biogenesis]].

To inhibit cell growth, the global rate of gene expression can be decreased or the global rate of [[biomolecular]] degradation can be increased by increasing the rate of [[autophagy]]. [[mTOR|TOR]] normally directly inhibits the function of the [[autophagy]] inducing kinase [[ULK1|Atg1/ULK1]]. Thus, reducing [[mTOR|TOR]] activity both reduces the global rate of [[translation (biology)|translation]] and increases the extent of [[autophagy]] to reduce cell growth.

== Cell growth regulation in animals ==
Many of the signal molecules that control of cellular growth are called [[growth factors]], many of which induce [[signal transduction]] via the [[PI3K/AKT/mTOR pathway]], which includes upstream lipid kinase [[Phosphoinositide 3-kinase|PI3K]] and the downstream serine/threonine protein [[kinase]] [[Akt/PKB signaling pathway|Akt]], which is able to activate another protein kinase [[mTOR|TOR]], which promotes [[Translation (biology)|translation]] and inhibits [[autophagy]] to drive cell growth.

Nutrient availability influences production of [[growth factors]] of the [[Insulin]]/[[IGF-1]] family, which circulate as hormones in animals to activate the [[PI3K/AKT/mTOR pathway]] in cells to promote [[mTOR|TOR]] activity so that when animals are well fed they will grow rapidly and when they are not able to receive sufficient nutrients they will reduce their growth rate. Recently it has been also demonstrated that cellular bicarbonate metabolism, which is responsible for cell growth, can be regulated by mTORC1 signaling.<ref>{{cite journal | vauthors = Ali E, Liponska A, O'Hara B, Amici D, Torno M, Gao P, Asara J, Yap M-N F, Mendillo M, Ben-Sahra I | title = The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis | journal = Molecular Cell | volume = 82 | issue = 1 | pages = 3284–3298.e7 | date = June 2022 | doi = 10.1016/j.molcel.2022.06.008 | pmid = 35772404 | pmc = 9444906 }}</ref>

In addition, the availability of [[amino acids]] to individual cells also directly promotes [[mTOR|TOR]] activity, although this mode of regulation is more important in single-celled organisms than in [[multicellular]] organisms such as animals that always maintain an abundance of [[amino acids]] in circulation.

One disputed theory proposes that many different mammalian cells undergo size-dependent transitions during the cell cycle. These transitions are controlled by the cyclin-dependent kinase Cdk1.<ref>{{cite book |doi=10.1016/S0074-7696(03)01004-0 |author=Mitchison JM |title=Growth During the Cell Cycle |journal=Int. Rev. Cytol. |volume=226 |pages=165–258 |year=2003 |pmid=12921238 |series=International Review of Cytology |isbn=978-0-12-364630-9 }}</ref> Though the proteins that control Cdk1 are well understood, their connection to mechanisms monitoring cell size remains elusive.

A postulated model for mammalian size control situates mass as the driving force of the cell cycle. A cell is unable to grow to an abnormally large size because at a certain cell size or cell mass, the S phase is initiated. The S phase starts the sequence of events leading to mitosis and cytokinesis. A cell is unable to get too small because the later cell cycle events, such as S, G2, and M, are delayed until mass increases sufficiently to begin S phase.<ref>{{cite journal|author=Cooper, Stephen|title= Control and maintenance of mammalian cell size|journal= BMC Cell Biology|volume= 5|issue= 1|pages= 35|doi=10.1186/1471-2121-5-35|pmid= 15456512|pmc= 524481|year= 2004|doi-access= free}}</ref>

== Cell populations ==
Cell populations go through a particular type of [[exponential growth]] called doubling or [[cell proliferation]]. Thus, each [[generation]] of cells should be twice as numerous as the previous generation. However, the number of generations only gives a maximum figure as not all cells survive in each generation. Cells can reproduce in the stage of Mitosis, where they double and split into two genetically equal cells.

== Cell size ==
Cell size is highly variable among organisms, with some algae such as ''[[Caulerpa taxifolia]]'' being a single cell several meters in length.<ref>{{cite news |last=Peplow |first=Mark |date=23 March 2005 |title=Algae create glue to repair cell damage |url=http://www.nature.com/news/2005/050321/full/news050321-11.html |newspaper=Nature.com |access-date=4 July 2016}}</ref> Plant cells are much larger than animal cells, and protists such as ''[[Paramecium]]'' can be 330 μm long, while a typical human cell might be 10 μm. How these cells "decide" how big they should be before dividing is an open question. Chemical gradients are known to be partly responsible, and it is hypothesized that mechanical stress detection by [[cytoskeletal]] structures is involved. Work on the topic generally requires an organism whose cell cycle is well-characterized.

=== Yeast cell size regulation ===
The relationship between cell size and [[cell division]] has been extensively studied in [[yeast]]. For some cells, there is a mechanism by which cell division is not initiated until a cell has reached a certain size. If the nutrient supply is restricted (after time t = 2 in the diagram, below), and the rate of increase in cell size is slowed, the time period between cell divisions is increased.<ref>{{cite journal |author1=Slavov N. |author2=Botstein D. |title=Coupling among Growth Rate Response, Metabolic Cycle and Cell Division Cycle in Yeast |journal=Molecular Biology of the Cell |volume=22 |pages=1997–2009|date=June 2011 |pmid=21525243 |doi=10.1091/mbc.E11-02-0132 |issue=12 |pmc=3113766}}</ref> Yeast cell-size mutants were isolated that begin cell division before reaching a normal/regular size (''wee'' mutants).<ref>''Wee1'' mutants of ''[[Schizosaccharomyces pombe|S. pombe]]'' have [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=Wee1+AND+mcb%5Bbook%5D+AND+106201%5Buid%5D&rid=mcb.section.3496#3501 small cell size] and the homologous proteins in humans also [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=Wee1+AND+mcb%5Bbook%5D+AND+106241%5Buid%5D&rid=mcb.section.3553#3562 regulate cell entry into mitosis]; in {{cite book
| veditors = Lodish HF, Berk A, Zipursky LS, Matsudaira P
| title = Molecular cell biology
| edition = 4th
| publisher = W.H. Freeman
| location = New York
| year = 2000
| isbn = 978-0-7167-3136-8
| display-editors = etal
| url-access = registration
| url = https://archive.org/details/molecularcellbio00lodi
}}</ref>
[[File:Cellcycle and growth.png|thumbnail|Figure 1:Cell cycle and growth]]

[[Wee1]] protein is a [[tyrosine kinase]] that normally phosphorylates the Cdc2 cell cycle regulatory protein (the homolog of [[CDK1]] in humans), a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. This [[covalent]] modification of the molecular structure of Cdc2 inhibits the enzymatic activity of Cdc2 and prevents cell division. Wee1 acts to keep Cdc2 inactive during early [[G2 phase|G2]] when cells are still small. When cells have reached sufficient size during G2, the phosphatase [[Cdc25]] removes the inhibitory phosphorylation, and thus activates Cdc2 to allow mitotic entry. A balance of Wee1 and Cdc25 activity with changes in cell size is coordinated by the mitotic entry control system. It has been shown in Wee1 mutants, cells with weakened Wee1 activity, that Cdc2 becomes active when the cell is smaller. Thus, mitosis occurs before the yeast reach their normal size. This suggests that cell division may be regulated in part by dilution of Wee1 protein in cells as they grow larger.

====Linking Cdr2 to Wee1====
The protein kinase [[CDR2 (gene)|Cdr2]] (which negatively regulates Wee1) and the Cdr2-related kinase [[CDR1 (gene)|Cdr1]] (which directly phosphorylates and inhibits Wee1 ''in vitro'')<ref>{{cite journal |vauthors=Wu L, Russell P |title=Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase |journal=Nature |volume=363 |issue=6431 |pages=738–41 |date=June 1993 |pmid=8515818 |doi=10.1038/363738a0|bibcode = 1993Natur.363..738W |s2cid=4320080 }}</ref> are localized to a band of cortical nodes in the middle of interphase cells. After entry into mitosis, cytokinesis factors such as [[myosin II]] are recruited to similar nodes; these nodes eventually condense to form the [[cytokinesis|cytokinetic]] ring.<ref>{{cite journal |doi=10.1016/S1534-5807(03)00324-1 |vauthors=Wu JQ, Kuhn JR, Kovar DR, Pollard TD |title=Spatial and temporal pathway for assembly and constriction of the contractile ring in fission yeast cytokinesis |journal=Dev. Cell |volume=5 |issue=5 |pages=723–34 |date=November 2003 |pmid=14602073 |doi-access=free }}</ref> A previously uncharacterized protein, [[leukotriene B4 receptor|Blt1]], was found to colocalize with Cdr2 in the medial interphase nodes. Blt1 knockout cells had increased length at division, which is consistent with a delay in mitotic entry. This finding connects a physical location, a band of cortical nodes, with factors that have been shown to directly regulate mitotic entry, namely Cdr1, Cdr2, and Blt1.

Further experimentation with [[green fluorescent protein|GFP]]-tagged proteins and mutant proteins indicates that the medial cortical nodes are formed by the ordered, Cdr2-dependent assembly of multiple interacting proteins during interphase. Cdr2 is at the top of this hierarchy and works upstream of Cdr1 and Blt1.<ref name=Moseley09>{{cite journal |vauthors=Moseley JB, Mayeux A, Paoletti A, Nurse P |title=A spatial gradient coordinates cell size and mitotic entry in fission yeast |journal=Nature |volume=459 |issue=7248 |pages=857–60 |date=June 2009 |pmid=19474789 |doi=10.1038/nature08074 |bibcode=2009Natur.459..857M|s2cid=4330336 }}</ref> Mitosis is promoted by the negative regulation of Wee1 by Cdr2. It has also been shown that Cdr2 recruits Wee1 to the medial cortical node. The mechanism of this recruitment has yet to be discovered. A Cdr2 kinase mutant, which is able to localize properly despite a loss of function in phosphorylation, disrupts the recruitment of Wee1 to the medial cortex and delays entry into mitosis. Thus, Wee1 localizes with its inhibitory network, which demonstrates that mitosis is controlled through Cdr2-dependent negative regulation of Wee1 at the medial cortical nodes.<ref name=Moseley09/>

==== Cell polarity factors ====
Cell polarity factors positioned at the cell tips provide spatial cues to limit Cdr2 distribution to the cell middle. In fission yeast ''[[Schizosaccharomyces pombe]]'' (''S. Pombe''), cells divide at a defined, reproducible size during mitosis because of the regulated activity of Cdk1.<ref>{{cite journal |doi=10.1016/S0168-9525(02)02745-2 |author=Rupes I |title=Checking cell size in yeast |journal=Trends Genet. |volume=18 |issue=9 |pages=479–85 |date=September 2002 |pmid=12175809 }}</ref> The cell polarity protein kinase [[Pom1]], a member of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) family of kinases, localizes to cell ends. In Pom1 knockout cells, Cdr2 was no longer restricted to the cell middle, but was seen diffusely through half of the cell. From this data it becomes apparent that Pom1 provides inhibitory signals that confine Cdr2 to the middle of the cell. It has been further shown that Pom1-dependent signals lead to the phosphorylation of Cdr2. Pom1 knockout cells were also shown to divide at a smaller size than wild-type, which indicates a premature entry into mitosis.<ref name=Moseley09/>

Pom1 forms polar gradients that peak at cell ends, which shows a direct link between size control factors and a specific physical location in the cell.<ref>{{cite journal |vauthors=Padte NN, Martin SG, Howard M, Chang F |title=The cell-end factor pom1p inhibits mid1p in specification of the cell division plane in fission yeast |journal=Curr. Biol. |volume=16 |issue=24 |pages=2480–7 |date=December 2006 |pmid=17140794 |doi=10.1016/j.cub.2006.11.024 |doi-access=free |bibcode=2006CBio...16.2480P }}</ref> As a cell grows in size, a gradient in Pom1 grows. When cells are small, Pom1 is spread diffusely throughout the cell body. As the cell increases in size, Pom1 concentration decreases in the middle and becomes concentrated at cell ends. Small cells in early G2 which contain sufficient levels of Pom1 in the entirety of the cell have inactive Cdr2 and cannot enter mitosis. It is not until the cells grow into late G2, when Pom1 is confined to the cell ends that Cdr2 in the medial cortical nodes is activated and able to start the inhibition of Wee1. This finding shows how cell size plays a direct role in regulating the start of mitosis. In this model, Pom1 acts as a molecular link between cell growth and mitotic entry through a Cdr2-Cdr1-Wee1-Cdk1 pathway.<ref name=Moseley09/> The Pom1 polar gradient successfully relays information about cell size and geometry to the Cdk1 regulatory system. Through this gradient, the cell ensures it has reached a defined, sufficient size to enter mitosis.

===Other experimental systems for the study of cell size regulation===
One common means to produce very large cells is by cell fusion to form [[syncytium|syncytia]]. For example, very long (several inches) [[skeletal muscle]] cells are formed by fusion of thousands of [[myocyte]]s. Genetic studies of the fruit fly ''[[Drosophila melanogaster|Drosophila]]'' have revealed several genes that are required for the formation of multinucleated muscle cells by fusion of [[myoblast]]s.<ref>{{cite journal
|vauthors=Menon SD, Osman Z, Chenchill K, Chia W | title = A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila
| journal = J. Cell Biol.
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| issue = 6
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|date=June 2005
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}}</ref> Some of the key proteins are important for [[cell adhesion]] between myocytes and some are involved in adhesion-dependent cell-to-cell [[signal transduction]] that allows for a cascade of cell fusion events.

Increases in the size of [[plant cell]]s are complicated by the fact that almost all plant cells are inside of a solid [[cell wall]]. Under the influence of certain plant hormones the cell wall can be remodeled, allowing for increases in cell size that are important for the growth of some plant tissues.

Most unicellular organisms are microscopic in size, but there are some giant [[bacterium|bacteria]] and [[protozoa]] that are visible to the naked eye. (See [https://web.archive.org/web/20040328112742/http://wikibooks.org/wiki/Biology_Cell_biology_Introduction_Cell_size Table of cell sizes]—Dense populations of a giant sulfur bacterium in Namibian shelf sediments<ref>{{cite journal |vauthors=Schulz HN, Brinkhoff T, Ferdelman TG, Mariné MH, Teske A, Jorgensen BB |s2cid=32571118 |title=Dense populations of a giant sulfur bacterium in Namibian shelf sediments |journal=Science |volume=284 |issue=5413 |pages=493–5 |date=April 1999 |pmid=10205058 |doi= 10.1126/science.284.5413.493|bibcode = 1999Sci...284..493S }}</ref>—[https://web.archive.org/web/20040427144107/http://www.bms.ed.ac.uk/research/others/smaciver/chaos.htm Large protists of the genus ''Chaos'', closely related to the genus ''Amoeba''].)

In the rod-shaped bacteria ''E. coli'', ''Caulobacter crescentus'' and ''B. subtilis'' cell size is controlled by a simple mechanisms in which cell division occurs after a constant volume has been added since the previous division.<ref>{{Cite journal
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 }}</ref> By always growing by the same amount, cells born smaller or larger than average naturally converge to an average size equivalent to the amount added during each generation.

==Cell division==

Cell reproduction is [[asexual reproduction|asexual]]. For most of the constituents of the cell, growth is a steady, continuous process, interrupted only briefly at [[M phase]] when the nucleus and then the cell divide in two.

The process of cell division, called [[cell cycle]], has four major parts called phases. The first part, called G<sub>1</sub> phase is marked by synthesis of various [[enzyme]]s that are required for DNA replication.
The second part of the cell cycle is the S phase, where [[DNA replication]] produces two identical sets of [[chromosomes]]. The third part is the G<sub>2</sub> phase in which a significant [[protein synthesis]] occurs, mainly involving the production of [[microtubules]] that are required during the process of division, called [[mitosis]].
The fourth phase, M phase, consists of nuclear division ([[karyokinesis]]) and cytoplasmic division ([[cytokinesis]]), accompanied by the formation of a new [[cell membrane]]. This is the physical division of mother and daughter cells. The M phase has been broken down into several distinct phases, sequentially known as [[prophase]], [[prometaphase]], [[metaphase]], [[anaphase]] and [[telophase]] leading to cytokinesis.

Cell division is more complex in [[eukaryote]]s than in other organisms. [[Prokaryote|Prokaryotic]] cells such as [[bacteria]]l cells reproduce by [[binary fission]], a process that includes DNA replication, chromosome segregation, and cytokinesis. Eukaryotic cell division either involves [[mitosis]] or a more complex process called [[meiosis]]. Mitosis and meiosis are sometimes called the two [[cell nucleus|nuclear]] division processes. Binary fission is similar to eukaryote cell reproduction that involves mitosis. Both lead to the production of two daughter cells with the same number of chromosomes as the parental cell. Meiosis is used for a special cell reproduction process of [[diploid]] organisms. It produces four special daughter cells ([[gamete]]s) which have half the normal cellular amount of DNA. A [[male]] and a [[female]] gamete can then combine to produce a [[zygote]], a cell which again has the normal amount of chromosomes.

The rest of this article is a comparison of the main features of the three types of cell reproduction that either involve binary fission, mitosis, or meiosis. The diagram below depicts the similarities and differences of these three types of cell reproduction.

[[File:Three cell growth types.svg|thumb|Cell growth]]

===Comparison of the three types of cell division===
The DNA content of a cell is duplicated at the start of the cell reproduction process. Prior to [[DNA replication]], the DNA content of a cell can be represented as the amount Z (the cell has Z chromosomes). After the DNA replication process, the amount of DNA in the cell is 2Z (multiplication: 2 x Z = 2Z). During Binary fission and mitosis the duplicated DNA content of the reproducing parental cell is separated into two equal halves that are destined to end up in the two daughter cells. The final part of the cell reproduction process is [[cell division]], when daughter cells physically split apart from a parental cell. During meiosis, there are two cell division steps that together produce the four daughter cells.

After the completion of binary fission or cell reproduction involving mitosis, each daughter cell has the same amount of DNA (Z) as what the parental cell had before it replicated its DNA. These two types of cell reproduction produced two daughter cells that have the same number of chromosomes as the parental cell. Chromosomes duplicate prior to cell division when forming new skin cells for reproduction. After meiotic cell reproduction the four daughter cells have half the number of chromosomes that the parental cell originally had. This is the [[haploid]] amount of DNA, often symbolized as N. Meiosis is used by [[diploid]] organisms to produce haploid gametes. In a diploid organism such as the human organism, most cells of the body have the diploid amount of DNA, 2N. Using this notation for counting chromosomes we say that human [[Somatic (biology)|somatic]] cells have [[Karyotype|46 chromosomes]] (2N = 46) while human [[Spermatozoon|sperm]] and [[Ovum|egg]]s have 23 chromosomes (N = 23). Humans have 23 distinct types of chromosomes, the 22 [[autosome]]s and the special category of [[Sex-determination system|sex chromosomes]]. There are two distinct sex chromosomes, the X chromosome and the Y chromosome. A diploid human cell has 23 chromosomes from that person's father and 23 from the mother. That is, your body has two copies of human chromosome number 2, one from each of your parents.
[[File:Single and double chromosomes.png|thumb|right|150px|Chromosomes]]
Immediately after DNA replication a human cell will have 46 "double chromosomes". In each double chromosome there are two copies of that chromosome's DNA molecule. During mitosis the double chromosomes are split to produce 92 "single chromosomes", half of which go into each daughter cell. During meiosis, there are two chromosome separation steps which assure that each of the four daughter cells gets one copy of each of the 23 types of chromosome.

===Sexual reproduction===
{{main|Evolution of sex}}
{{further|Origin and function of meiosis|Homologous recombination}}
Though cell reproduction that uses mitosis can reproduce eukaryotic cells, eukaryotes bother with the more complicated process of meiosis because [[sexual reproduction]] such as meiosis confers a [[Natural selection|selective advantage]]. Notice that when meiosis starts, the two copies of sister chromatids number 2 are adjacent to each other. During this time, there can be [[genetic recombination]] events. Information from the chromosome 2 DNA gained from one parent (red) will transfer over to the chromosome 2 DNA molecule that was received from the other parent (green). Notice that in mitosis the two copies of chromosome number 2 do not interact. [[Homologous recombination|Recombination of genetic information between homologous chromosomes]] during [[meiosis]] is a process for [[DNA repair|repairing DNA damages]]. This process can also produce new combinations of genes, some of which may be adaptively beneficial and influence the course of evolution. However, in organisms with more than one set of chromosomes at the main life cycle stage, sex may also provide an advantage because, under random mating, it produces [[homozygote]]s and [[heterozygote]]s according to the [[Hardy–Weinberg ratio]].

== Disorders ==
A series of growth disorders can occur at the cellular level and these consequently underpin much of the subsequent course in [[cancer]], in which a group of cells display uncontrolled growth and division beyond the normal limits, ''invasion'' (intrusion on and destruction of adjacent tissues), and sometimes ''[[metastasis]]'' (spread to other locations in the body via lymph or blood). Several key determinants of cell growth, like [[ploidy]] and the regulation of cellular [[metabolism]], are commonly disrupted in [[tumors]].<ref name=Schmoller2015>{{cite journal |last1=Schmoller |first1=Kurt M. |last2=Skotheim |first2=Jan M.|title=The Biosynthetic Basis of Cell Size Control |journal=Trends Cell Biol.|date=December 2015 |volume=25 |issue=12 |pages=793–802|doi=10.1016/j.tcb.2015.10.006|pmid=26573465|pmc=6773270 }}</ref> Therefore, heterogenous cell growth and [[pleomorphism (cytology)|pleomorphism]] is one of the earliest hallmarks of [[cancer]] progression.<ref name=Travis2015>{{cite book|last1=Travis|first1=W.D.|last2=Brambilla|first2=B.|last3=Burke|first3=A.P|last4=Marx |first4=A.|last5=Nicholson|first5=A.G.|title=WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart|url=https://apps.who.int/bookorders/anglais/detart1.jsp?codlan=1&codcol=70&codcch=4007|location= Lyon|publisher=International Agency for Research on Cancer|isbn=978-92-832-2436-5|year=2015}}</ref><ref name=El-Naggar2017>{{cite book|last1=El-Naggar|first1=A.K.|last2=Chan|first2=J.C.K.|last3=Grandis|first3=J.R.|last4=Takata|first4=T.|last5=Slootweg|first5=P.J.|title=WHO Classification of Head and Neck Tumours|url=http://publications.iarc.fr/Book-And-Report-Series/Who-Iarc-Classification-Of-Tumours/Who-Classification-Of-Head-And-Neck-Tumours-2017|location=Lyon|publisher=International Agency for Research on Cancer (also known as Adman)|isbn=978-92-832-2438-9|date=2017-01-23|access-date=2019-10-31|archive-url=https://web.archive.org/web/20191031140552/http://publications.iarc.fr/Book-And-Report-Series/Who-Iarc-Classification-Of-Tumours/Who-Classification-Of-Head-And-Neck-Tumours-2017|archive-date=2019-10-31|url-status=dead}}</ref> Despite the prevalence of pleomorphism in human pathology, its role in disease progression is unclear. In [[epithelial]] tissues, misregulation of cellular size can induce packing defects and disperse aberrant cells.<ref name=Ramanathan2019>{{cite journal |last1=Ramanathan |first1=Subramanian P. |last2=Krajnc |first2=Matej |last3=Gibson |first3=Matthew C. |title=Cell-Size Pleomorphism Drives Aberrant Clone Dispersal in Proliferating Epithelia |journal=Developmental Cell |date=October 2019 |volume=51 |issue=1 |pages=49–61.e4 |doi=10.1016/j.devcel.2019.08.005 |pmid=31495693 |pmc=6903429 }}</ref> But the consequence of atypical cell growth in other animal tissues is unknown.

== Measurement methods ==
The cell growth can be detected by a variety of methods.
The cell size growth can be visualized by [[microscopy]], using suitable stains. But the increase of cells number is usually more significant. It can be measured by manual counting of cells under microscopy observation, using the dye exclusion method (i.e. [[trypan blue]]) to count only viable cells. Less fastidious, scalable, methods include the use of [[cytometer]]s, while [[flow cytometry]] allows combining cell counts ('events') with other specific parameters: fluorescent probes for membranes, cytoplasm or nuclei allow distinguishing dead/viable cells, cell types, cell differentiation, expression of a [[biomarker]] such as [[Ki-67 (protein)|Ki67]]. The total mass of a cell, which comprises the mass of all its components including its water content, is a dynamic magnitude and it can be measured in real-time and tracked over hours or even days using an inertial picobalance.<ref>{{Cite journal |last1=Martínez-Martín |first1=David |last2=Fläschner |first2=Gotthold |last3=Gaub |first3=Benjamin |last4=Martin |first4=Sascha |last5=Newton |first5=Richard |last6=Beerli |first6=Corina |last7=Mercer |first7=Jason |last8=Gerber |first8=Christoph |last9=Müller |first9=Daniel J. |date=October 2017 |title=Inertial picobalance reveals fast mass fluctuations in mammalian cells |url=https://www.nature.com/articles/nature24288 |journal=Nature |language=en |volume=550 |issue=7677 |pages=500–505 |doi=10.1038/nature24288 |pmid=29072271 |bibcode=2017Natur.550..500M |issn=1476-4687}}</ref><ref>{{Cite journal |last1=Cuny |first1=Andreas P. |last2=Tanuj Sapra |first2=K. |last3=Martinez-Martin |first3=David |last4=Fläschner |first4=Gotthold |last5=Adams |first5=Jonathan D. |last6=Martin |first6=Sascha |last7=Gerber |first7=Christoph |last8=Rudolf |first8=Fabian |last9=Müller |first9=Daniel J. |date=2022-06-22 |title=High-resolution mass measurements of single budding yeast reveal linear growth segments |journal=Nature Communications |language=en |volume=13 |issue=1 |pages=3483 |doi=10.1038/s41467-022-30781-y |issn=2041-1723 |pmc=9217925 |pmid=35732645|bibcode=2022NatCo..13.3483C }}</ref> A cell's buoyant mass, which corresponds to the total mass of the cell minus that of the fluid it displaces, can be measured using suspended microchannel resonators.<ref>{{Cite journal |last1=Burg |first1=Thomas P. |last2=Godin |first2=Michel |last3=Knudsen |first3=Scott M. |last4=Shen |first4=Wenjiang |last5=Carlson |first5=Greg |last6=Foster |first6=John S. |last7=Babcock |first7=Ken |last8=Manalis |first8=Scott R. |date=April 2007 |title=Weighing of biomolecules, single cells and single nanoparticles in fluid |url=https://www.nature.com/articles/nature05741 |journal=Nature |language=en |volume=446 |issue=7139 |pages=1066–1069 |doi=10.1038/nature05741 |pmid=17460669 |bibcode=2007Natur.446.1066B |hdl=11858/00-001M-0000-0014-9C58-F |issn=1476-4687|hdl-access=free }}</ref>

Beside the increasing number of cells, one can be assessed regarding the metabolic activity growth, that is, the [[Carboxyfluorescein diacetate|CFDA]] and [[calcein]]-AM measure (fluorimetrically) not only the membrane functionality (dye retention), but also the functionality of cytoplasmic enzymes (esterases). The [[MTT assay]]s (colorimetric) and the [[resazurin]] assay (fluorimetric) dose the mitochondrial redox potential.

All these assays may correlate well, or not, depending on cell growth conditions and desired aspects (activity, proliferation). The task is even more complicated with populations of different cells, furthermore when combining cell growth interferences or [[toxicity]].

== See also ==
* [[Bacterial growth]]

== References ==
{{reflist|30em}}

== Books ==
* {{cite book |last1=Morgan |first1=David O. |title=The cell cycle: principles of control |date=2007 |publisher=Sunderland, Mass. |location=London |isbn=978-0-9539181-2-6}}

== External links ==
* [http://members.optusnet.com.au/exponentialist/Cells.htm A comparison of generational and exponential models of cell population growth]
* [http://demonstrations.wolfram.com/LocalGrowthInAnArrayOfDisks/ Local Growth in an Array of Disks] ''Wolfram Demonstrations Project''

[[Category:Cell cycle]]
[[Category:Cellular processes]]