Mitotic cell rounding is a shape change that occurs in most

animal cell The cell is the basic structural and functional unit of all life, forms of life. Every cell consists of cytoplasm enclosed within a Cell membrane, membrane; many cells contain organelles, each with a specific function. The term comes from the ...

s that undergo

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

. Cells abandon the spread or elongated shape characteristic of

interphase Interphase is the active portion of the cell cycle that includes the G1, S, and G2 phases, where the cell grows, replicates its DNA, and prepares for mitosis, respectively. Interphase was formerly called the "resting phase," but the cell i ...

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'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' 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, an ...

''.

Early observations

In 1935, one of the first published accounts of mitotic rounding in live tissue described cell rounding in the pseudostratified epithelium 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 folds become elevated, ...

. Sauer noticed that cells in mitosis rounded up to the apical, 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 and

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

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 is 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 process ...

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 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 a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

invagination of the ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), 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", "pomace fly" ...

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

Zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...

. * 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 Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the opti ...

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

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 Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...

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 Hydrostatics is the branch of fluid mechanics that studies fluids at hydrostatic equilibrium and "the pressure in a fluid or exerted by a fluid on an immersed body". The word "hydrostatics" is sometimes used to refer specifically to water and o ...

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 unsupported at 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 cantilev ...

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

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

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

HeLa cells HeLa () is an immortalized cell line used in scientific research. It is the oldest human cell line and one of the most commonly used. HeLa cells are durable and prolific, allowing for extensive applications in scientific study. The line is ...

''in vitro'', the force generated by a half-deformed mitotic cell is on the order of 50 to 100 nano

newtons The newton (symbol: N) is the unit of force in the International System of Units (SI). Expressed in terms of SI base units, it is 1 kg⋅m/s2, the force that accelerates a mass of one kilogram at one metre per second squared. The unit i ...

. Internal hydrostatic pressure has been measured to increase from below 100 pascals in

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 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 ...

. 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 DJ1, also known as Parkinson disease protein 7, is a protein which in humans is encoded by the ''PARK7'' gene. Its weak glyoxalase activity has been verified by many labs, however the reported protein deglycase activity is likely to be an artifact ...

and FAM134A/RETREG2.

References

External links

* * *{{cite web, url=https://www.youtube.com/watch?v=_1CxNZX4cW4, title=Two Minute Talk: Mitotic Cell Rounding — YouTube, date=28 July 2014 , publisher=youtube.com, accessdate=2015-07-04 Cell biology