Mitotic cell rounding is a shape change that occurs in most

animal cell Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacter ...

s that undergo mitosis. Cells abandon the spread or elongated shape characteristic of

interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...

and contract into a spherical morphology during mitosis. The phenomenon is seen both in artificial cultures ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

'' and naturally forming tissue ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

''.

Early observations

In 1935, one of the first published accounts of mitotic rounding in live tissue described cell rounding in the

pseudostratified epithelium A pseudostratified epithelium is a type of epithelium that, though comprising only a single layer of cells, has its cell nuclei positioned in a manner suggestive of stratified epithelia. As it rarely occurs as squamous or cuboidal epithelia ...

of the mammalian

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, ...

. Sauer noticed that cells in mitosis rounded up to the

apical Apical means "pertaining to an apex". It may refer to: *Apical ancestor, refers to the last common ancestor of an entire group, such as a species (biology) or a clan (anthropology) *Apical (anatomy), an anatomical term of location for features loc ...

, or luminal, surface of the columnar epithelium before dividing and returning to their elongated

morphology Morphology, from the Greek and meaning "study of shape", may refer to: Disciplines * Morphology (archaeology), study of the shapes or forms of artifacts * Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...

Significance

For a long time it was not clear why cells became round in mitosis. Recent studies in the

epithelia Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

and epidermis of various organisms, however, show that mitotic cell rounding might serve several important functions. * Firstly, mitotic cell rounding in combination with maintenance of apical cell-cell junctions appears to be necessary for correct

mitotic spindle In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...

alignment, so that daughter cells divide parallel to the tissue plane, thus sharing apical surface to maintain tissue homeostasis. Failure to achieve this may result in mislocalization of one daughter cell to the basal region on the tissue layer and clearance via

apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes incl ...

cell death. * Secondly, mitotic rounding has been proposed to be a driver for morphological events during tissue development. Examples include

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...

invagination of the ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

'' tracheal placode and the anisotropic shape and growth of the inner ear lumen in

Zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ca ...

. * Thirdly, mitotic rounding has been shown to be important to generate sufficient space and appropriate geometry for proper mitotic spindle function, which is necessary for timely and accurate progression through mitosis. Thus, mitotic cell rounding is involved in tissue organization and homeostasis.

Mechanisms

To understand the physical mechanisms of how cells round up in mitosis, researchers have conducted mechanical measurements with cultured cells ''

''. The forces that drive cell rounding have recently been characterized by researchers from the groups of Professors Tony Hyman and Daniel Muller, who used flat atomic force microscopy

cantilevers A cantilever is a rigid structural element that extends horizontally and is supported at only one end. Typically it extends from a flat vertical surface such as a wall, to which it must be firmly attached. Like other structural elements, a canti ...

to constrain mitotic cells and measure the response force. More than 90% of the forces are generated by the collective activity of

myosin II Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin (M2 ...

molecular motor Molecular motors are natural (biological) or artificial molecular machines that are the essential agents of movement in living organisms. In general terms, a motor is a device that consumes energy in one form and converts it into motion or mech ...

s in the actin cortex. As a result, the surface tension and effective stiffness of the actin cortex increase as has been consistently observed in mitotic cells. This in turn yields an increase in

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

hydrostatic pressure Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body " fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an imm ...

due to the Law of Laplace, which relates surface tension of a fluid interface to the differential pressure sustained across that interface. The increase in hydrostatic pressure is important because it produces the outward force necessary to push and rounds up against external objects or impediments, such as flexible

cantilever A cantilever is a rigid structural element that extends horizontally and is supported at only one end. Typically it extends from a flat vertical surface such as a wall, to which it must be firmly attached. Like other structural elements, a cant ...

, soft

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...

or micropillar (''in vitro'' examples), or surrounding

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...

and neighboring cells (''in vivo'' examples). In

HeLa cells HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta L ...

''in vitro'', the force generated by a half-deformed mitotic cell is on the order of 50 to 100 nano newtons. Internal hydrostatic pressure has been measured to increase from below 100

pascals The pascal (symbol: Pa) is the unit of pressure in the International System of Units (SI), and is also used to quantify internal pressure, stress, Young's modulus, and ultimate tensile strength. The unit, named after Blaise Pascal, is defined ...

to 3 to 10 fold that in mitosis. In similar ''in vitro'' experiments, it was found that the threshold forces required to prevent mitosis are in excess of 100 nN. At threshold forces the cell suffers a loss of cortical F-actin uniformity, which further amplifies the susceptibility to applied force. These effects potentiate distortion of cell dimensions and subsequent perturbation of mitotic progression via spindle defects. Release of stable

focal adhesions In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...

is another important aspect of mitotic rounding. Cells that are genetically perturbed to manifest constitutively active adhesion regulators are unable to properly remodel their focal adhesions and facilitate the generation of a uniform actomyosin cortex. Overall, the biochemical events governing the morphological and mechanical changes in mitotic cells are orchestrated by the mitotic master regulator

Cdk1 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in t ...

. Apart from actomyosin-related genes, several disease genes have recently been implicated in mitotic cell rounding. These include Parkinson’s disease associated DJ-1/ Park7 and FAM134A/RETREG2.

References

External links

* * *{{cite web, url=https://www.youtube.com/watch?v=_1CxNZX4cW4, title=Two Minute Talk: Mitotic Cell Rounding — YouTube, publisher=youtube.com, accessdate=2015-07-04 Cell biology