Cell migration is a central process in the development and maintenance of multicellular organisms. Multicellular organisms are Organisms consisting of more than one cell, and having Differentiated cells that perform specialized functions Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in a particular direction to a specific location. Embryogenesis is the process by which the Embryo is formed and develops Wound healing, or wound repair, is the body's natural process of regenerating dermal and epidermal tissue. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Errors during this process have serious consequences, including mental retardation, vascular disease, tumor formation and metastasis. Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and See also Cancer A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling , for example, invasive tumour cells. Cells in animal tissues often migrate in response to, and towards, specific external signals, a process called chemotaxis. Chemotaxis, a kind of Taxis, is the phenomenon in which bodily cells bacteria, and other single-cell or Multicellular organisms direct their movements

Studying cell migration

The migration of single mammalian cells is usually viewed in the microscope as the cells move randomly on a glass slide. As the actual movement is very slow — usually a few micrometers/minute — time-lapse films are taken so that a speeded up movie can be viewed (see the movie of MDBK cells moving over a glass slide). Time-lapse photography is a Cinematography technique whereby each Film frame is captured at a rate much slower than it will be played back This shows that, although the shape of a moving cell varies considerably, its leading front has a characteristic behaviour. This region of the cell is highly active, sometimes spreading forwards quickly, sometimes retracting, sometimes ruffling or bubbling. It is generally accepted that the leading front is the main motor which pulls the cell forward.

Common features

There is still great uncertainty of how cell migration really works. However, because the locomotion of all mammalian cells (except sperm) has several common features, the underlying processes are believed to be similar. A spermatozoon or spermatozoan ( pl spermatozoa) from the Ancient Greek σπέρμα (seed and ζῷον (living being and more commonly known The two main constant features are: (1) the behaviour of the leading front. (2) the observation that any debris on the dorsal surface of the cell moves backwards on the cell’s surface towards its trailing end. The latter feature is most easily observed when aggregates of a surface molecule are cross-linked with a fluorescent antibody (see cap formation) or when small beads become artificially bound to the front of the cell. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily When Molecules on the surface of a cell are Crosslinked they are moved to one end of the cell to form a “cap”

Besides mammalian cells, many other eukaryotic cells appear to move in a similar way. Thus, one of the most valuable model creatures for studying locomotion and chemotaxis is the amoeba Dictyostelium discoideum. Dictyostelium discoideum is a species of soil-living amoeba belonging to the group Mycetozoa.

Molecular processes at the front

There are two main theories of how the cell stretches forward in the front edge, namely the cytoskeletal model and membrane flow model. It is not impossible that both contribute to the movement.

Two different models for how cells move. A) Cytoskeletal model. B) Membrane Flow Model

Cytoskeletal model (A)

The front is a site of rapid actin polymerisation: soluble actin monomers polymerise to form filaments. Actin is a globular roughly 42-kDa Protein found in all eukaryotic cells (except for Nematode sperm where it may be present at concentrations of This has led to the view that it is the formation of these actin filaments which pushes the leading front forward and is the main motile force for advancing the cell’s front.

Membrane flow model (B)

Studies have also shown that the front is the site at which membrane is returned to the cell surface from internal membrane pools at the end of the endocytic cycle. Most animal cells take up portions of their surface Plasma membranes in a process called Endocytosis. This has led to the view that extension of the leading edge occurs primarily by addition of membrane at the front of the cell. If so, the actin filaments which form at the front might stabilise the added membrane so that a structured extension, or lamella, is formed rather than the cell blowing bubbles at its front. For a cell to move, it is necessary to bring a fresh supply of feet — those molecules, called integrins, which attach a cell to the surface on which it is crawling — to the front. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. It is likely that these feet are brought to the front by the membrane added there. Those coated pits could be formed by caveolins.

The nucleus and rear

Given that a cell’s front advances, what about the rest of the cell? Is it simply dragged forward, like a sack? We do not know, but there are suggestions that the nucleus and perhaps other large structures inside the cell may also be pulled forward by actin filaments. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed In addition, it may be that the rear of the cell actively contracts, as it is here that, in some cells, the major contractile protein myosin is found. Myosins are a large family of Motor proteins found in Eukaryotic tissues.

Mutants

Insight into how complex biological processes work can often be gleaned from a study of mutations. In the case of the intracellular mechanisms underlying cell movement, this has been largely unsuccessful. Thus, although many mutants are known in Drosophila which affect migratory processes, these tend to fall into two groups: transcription factors (such as slow border cells (slbo) which affects the migration of the border cells) or key regulator proteins (such as C-Jun N-terminal kinases (JNK) which controls dorsal closure). Drosophila is a Genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" For the cells produced by plant roots that are also known as border cells see Root. See also Mitogen-activated protein kinase c-Jun N-terminal kinases (JNKs originally identified as Kinases that bind and Phosphosphorylate C-Jun These, however, tell us little about how cells actually move.

Another major source of mutants is the haploid amoeba Dictyostelium. "Haplo" redirects here For the fictional character see The Death Gate Cycle. Many single copy genes associated with cytoskeletal function have been deleted: these mutants usually have only a weak phenotype, suggesting either that these genes are not required for locomotion or that there are multiple mechanisms by which cells can move. A phenotype is any observable characteristic of an Organism, such as its morphology, Development, biochemical or physiological properties However, temperature-sensitive mutants in the genes for N-ethylmaleimide sensitive fusion protein (NSF) and Sec1 rapidly block cell migration indicating that the NSF protein and Sec1p are both required for some aspect of cell movement. N-ethylmaleimide-sensitive factor, also known as NSF or N-ethylmaleimide sensitive fusion proteins, is a human Gene. NSF is known to function in intracellular membrane fusion; Sec1p in yeast is required for polarised exocytosis.

Cell polarity

Migrating cells clearly have a polarity: a front and a back. How this arrow is formulated at a molecular level inside a cell is unknown. In a cell which is meandering in a random way, the front can easily give way to become passive as some other region of the cell forms a new front. In chemotaxing cells, the stability of the front is enhanced and the cell seems purposively to advance towards its target. This polarity is reflected at a molecular level by a restriction of certain molecules to particular regions of the cell surface: thus the phospholipid PIP3 and activated Rac and CDC42 are found at the front of the cell, whereas Rho GTPase and PTEN are found towards the rear. Phosphatidylinositol (345-trisphosphate (PtdIns(345 P 3 commonly abbreviated to PIP3 is the product of the class I Phosphoinositide CDC42 is a protein involved in regulation of the Cell cycle. PTEN ( phosphatase and tensin homolog) gene is a Human Gene that acts as a Tumor suppressor gene, (i

It is believed that microtubules and filamentous actin are important for establishing and maintaining a cell’s polarity. Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers Thus, drugs which destroy microtubules disrupt the polarity of many cells; drugs which destroy actin filaments have multiple and complex effects. It may be that, as part of the locomotory process, membrane vesicles are transported along these filaments to the cell’s front. A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed In chemotaxing cells, the increased persistence of migration towards the target may result from an increased stability of the arrangement of the filamentous structures inside the cell and which determine its polarity. In turn, these filamentous structures may be arranged inside the cell according to how molecules like PIP3 and PTEN are arranged on the inner cell surface. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer And where these are located appears in turn to be determined by the chemoattractant signals as these impinge on specific receptors on the cell’s outer surface. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling

References

• A cell's sense of direction
• Membrane Flow and the Cytoskeleton Cooperate in Moving Cells
• Cell Migration: Integrating signals from front to back
• Regulation of microtubules in cell migration
• Cell Migration Gateway The Cell Migration Gateway is a comprehensive and regularly updated resource on cell migration
• Cell Migration 101 A Primer on Cell Migration
• Cell Migration Knowledgebase: A comprehensive database of cell migration related proteins, families, complexes and othologs

See also

• Endocytic cycle
• Cap formation
• Neurophilia