Chemotaxis

Positive chemotaxis occurs if the movement is toward a higher concentration of the chemical in question; negative chemotaxis if the movement is in the opposite direction. Chemically prompted kinesis (randomly directed or nondirectional) can be called chemokinesis.

History of chemotaxis research

Although migration of cells was detected from the early days of the development of microscopy by

Some bacteria, such as E. coli, have several flagella per cell (4–10 typically). These can rotate in two ways:

1. Counter-clockwise rotation aligns the flagella into a single rotating bundle, causing the bacterium to swim in a straight line; and
2. Clockwise rotation breaks the flagella bundle apart such that each flagellum points in a different direction, causing the bacterium to tumble in place.^[15]

The directions of rotation are given for an observer outside the cell looking down the flagella toward the cell.^[16]

Behavior

The overall movement of a bacterium is the result of alternating tumble and swim phases, called run-and-tumble motion.^[17] As a result, the trajectory of a bacterium swimming in a uniform environment will form a random walk with relatively straight swims interrupted by random tumbles that reorient the bacterium.^[18] Bacteria such as E. coli are unable to choose the direction in which they swim, and are unable to swim in a straight line for more than a few seconds due to rotational diffusion; in other words, bacteria "forget" the direction in which they are going. By repeatedly evaluating their course, and adjusting if they are moving in the wrong direction, bacteria can direct their random walk motion toward favorable locations.^[19]

In the presence of a chemical gradient bacteria will chemotax, or direct their overall motion based on the gradient. If the bacterium senses that it is moving in the correct direction (toward attractant/away from repellent), it will keep swimming in a straight line for a longer time before tumbling; however, if it is moving in the wrong direction, it will tumble sooner. Bacteria like E. coli use temporal sensing to decide whether their situation is improving or not, and in this way, find the location with the highest concentration of attractant, detecting even small differences in concentration.^[20]

This biased random walk is a result of simply choosing between two methods of random movement; namely tumbling and straight swimming.^[21] The helical nature of the individual flagellar filament is critical for this movement to occur. The protein structure that makes up the flagellar filament, flagellin, is conserved among all flagellated bacteria.^[22] Vertebrates seem to have taken advantage of this fact by possessing an immune receptor (TLR5) designed to recognize this conserved protein. ^[23]

As in many instances in biology, there are bacteria that do not follow this rule. Many bacteria, such as Vibrio, are monoflagellated and have a single flagellum at one pole of the cell. Their method of chemotaxis is different. Others possess a single flagellum that is kept inside the cell wall. These bacteria move by spinning the whole cell, which is shaped like a corkscrew.^{[24][page needed]}

Signal transduction

Chemical gradients are sensed through multiple

Receptors

In general, eukaryotic cells sense the presence of chemotactic stimuli through the use of 7-transmembrane (or serpentine) heterotrimeric

• Formyl peptides - formyl peptide receptors (FPR),
• Chemokines - chemokine receptors
  (CCR or CXCR), and
• Leukotrienes - leukotriene receptors (BLT).^[58]

While some chemotaxis receptors are expressed in the surface membrane with long-term characteristics, as they are determined genetically, others have short-term dynamics, as they are assembled ad hoc in the presence of the ligand.^[60] The diverse features of the chemotaxis receptors and ligands allows for the possibility of selecting chemotactic responder cells with a simple chemotaxis assay By chemotactic selection, we can determine whether a still-uncharacterized molecule acts via the long- or the short-term receptor pathway.^[61] The term chemotactic selection is also used to designate a technique that separates eukaryotic or prokaryotic cells according to their chemotactic responsiveness to selector ligands.^{[62][non-primary source needed][non-primary source needed]}

Chemotactic ligands

The number of molecules capable of eliciting chemotactic responses is relatively high, and we can distinguish primary and secondary chemotactic molecules.^{[citation needed]} The main groups of the primary ligands are as follows:

• Formyl peptides are di-, tri-, tetrapeptides of bacterial origin, formylated on the N-terminus of the peptide.[
  Formyl peptide receptors
  .
• Complement 3a (
  C3a) and complement 5a (C5a) are intermediate products of the complement cascade.^{[citation needed]} Their synthesis is joined to the three alternative pathways (classical, lectin-dependent, and alternative) of complement activation by a convertase enzyme.^{[citation needed]} The main target cells of these derivatives are neutrophil granulocytes and monocytes as well.^{[citation needed}
  ]
• RANTES), and CXC chemokines are neutrophil granulocyte-specific (e.g., IL-8).^{[citation needed]} Investigations of the three-dimensional structures of chemokines provided evidence that a characteristic composition of beta-sheets and an alpha helix provides expression of sequences required for interaction with the chemokine receptors.^{[citation needed]} Formation of dimers and their increased biological activity was demonstrated by crystallography of several chemokines, e.g. IL-8.^{[citation needed}
  ]
• Metabolites of
  polyunsaturated fatty acids
  • BLT2, which are highly expressed in cells involved in inflammation and allergy.^[64]
  • The family of
    bacterial
    infections. After leaving nearby blood vessels, these cells recognize chemicals produced by bacteria in a cut or scratch and migrate "toward the smell".
  • 5-hydroxyeicosatrienoic acid and 5-oxoeicosatrienoic acid are metabolites of Mead acid (5Z,8Z,11Z-eicosatrirenoid acid); they stimulate leukocyte chemotaxis through the oxoeicosanoid receptor 1^[65] with 5-oxoeicosatrienoic acid being as potent as its arachidonic acid-derived analog, 5-oxo-eicosatetraenoic acid, in stimulating human blood eosinophil and neutrophil chemotaxis.^[64]
  • 12-Hydroxyeicosatetraenoic acid is an eicosanoid metabolite of arachidonic acid made by ALOX12 which stimulates leukocyte chemotaxis through the leukotriene B4 receptor, BLT2.^[64]
  • cyclooxygenase 2 that stimulates chemotaxis through the Prostaglandin DP2 receptor. It elicits chemotactic responses in eosinophils, basophils, and T helper cells of the Th2 subtype.^{[66][non-primary source needed][non-primary source needed}
    ]
  • 12-Hydroxyheptadecatrienoic acid is a non-eicosanoid metabolite of arachidonic acid made by cyclooxygenase 1 or cyclooxygenase 2 that stimulates leukocyte chemotaxis though the leukotriene B4 receptor, BLT2.^{[67][non-primary source needed][non-primary source needed]}
  • 15-oxo-eicosatetraenoic acid is an eicosanoid metabolite of arachidonic acid made my ALOX15; it has weak chemotactic activity for human monocytes (sees 15-Hydroxyeicosatetraenoic acid#15-oxo-ETE).^{[68][non-primary source needed][non-primary source needed]} The receptor or other mechanism by which this metabolite stimulates chemotaxis has not been elucidated.

Chemotactic range fitting

Chemotactic range fitting

Chemotactic responses elicited by

chemorepellent activities have narrow ranges.^[69]

Clinical significance

A changed migratory potential of cells has relatively high importance in the development of several clinical symptoms and syndromes. Altered chemotactic activity of extracellular (e.g., Escherichia coli) or intracellular (e.g., Listeria monocytogenes) pathogens itself represents a significant clinical target. Modification of endogenous chemotactic ability of these microorganisms by pharmaceutical agents can decrease or inhibit the ratio of infections or spreading of infectious diseases. Apart from infections, there are some other diseases wherein impaired chemotaxis is the primary etiological factor, as in Chédiak–Higashi syndrome, where giant intracellular vesicles inhibit normal migration of cells.

Chemotaxis in diseases^{[citation needed]}

Type of disease	Chemotaxis increased	Chemotaxis decreased
Infections	Inflammations	AIDS, Brucellosis
Chemotaxis results in the disease	—	Kartagener syndrome
Chemotaxis is affected	metastatic tumors	Hodgkin disease, male infertility
Intoxications	benzpyrene	Hg and Cr salts, ozone

Mathematical models

Several mathematical models of chemotaxis were developed depending on the type of

• Migration (e.g., basic differences of bacterial swimming, movement of unicellular eukaryotes with
  amoeboid
  migration)
• Physico-chemical characteristics of the chemicals (e.g., diffusion) working as ligands
• Biological characteristics of the ligands (attractant, neutral, and repellent molecules)
• Assay systems applied to evaluate chemotaxis (see incubation times, development, and stability of concentration gradients)
• Other environmental effects possessing direct or indirect influence on the migration (lighting, temperature, magnetic fields, etc.)

Although interactions of the factors listed above make the behavior of the solutions of mathematical models of chemotaxis rather complex, it is possible to describe the basic phenomenon of chemotaxis-driven motion in a straightforward way. Indeed, let us denote with ${\displaystyle \varphi }$ the spatially non-uniform concentration of the chemo-attractant and ${\displaystyle \nabla \varphi }$ as its gradient. Then the chemotactic cellular flow (also called current) ${\displaystyle {\bf {J}}}$ that is generated by the chemotaxis is linked to the above gradient by the law:^[70]

${\displaystyle {\bf {J}}=C\chi (\varphi )\nabla \varphi }$

where ${\displaystyle C}$ is the spatial density of the cells and ${\displaystyle \chi }$ is the so-called 'Chemotactic coefficient' - ${\displaystyle \chi }$ is often not constant, but a decreasing function of the chemo-attractant. For some quantity ${\displaystyle \rho }$ that is subject to total flux ${\displaystyle {\bf {J}}}$ and generation/destruction term ${\displaystyle S}$, it is possible to formulate a continuity equation:

${\displaystyle {\partial \rho \over {\partial t}}+\nabla \cdot {\bf {J}}=S}$

where ${\displaystyle \nabla \cdot ()}$ is the divergence. This general equation applies to both the cell density and the chemo-attractant. Therefore, incorporating a diffusion flux into the total flux term, the interactions between these quantities are governed by a set of coupled reaction-diffusion partial differential equations describing the change in ${\displaystyle C}$ and ${\displaystyle \varphi }$:^[70]

${\displaystyle {\begin{aligned}{\partial C \over {\partial t}}&=f(C)+\nabla \cdot \left[D_{C}\nabla C-C\chi (\varphi )\nabla \varphi \right]\\{\partial \varphi \over {\partial t}}&=g(\varphi ,C)+\nabla \cdot (D_{\varphi }\nabla \varphi )\end{aligned}}}$

where ${\displaystyle f(C)}$ describes the growth in cell density, ${\displaystyle g(\varphi ,C)}$ is the kinetics/source term for the chemo-attractant, and the diffusion coefficients for cell density and the chemo-attractant are respectively ${\displaystyle D_{C}}$ and ${\displaystyle D_{\varphi }}$.

Spatial ecology of soil microorganisms is a function of their chemotactic sensitivities towards substrate and fellow organisms.^{[71][non-primary source needed][non-primary source needed]} The chemotactic behavior of the bacteria was proven to lead to non-trivial population patterns even in the absence of environmental heterogeneities. The presence of structural pore scale heterogeneities has an extra impact on the emerging bacterial patterns.

Measurement of chemotaxis

Main article: Chemotaxis assay

A wide range of techniques is available to evaluate chemotactic activity of cells or the chemoattractant and chemorepellent character of ligands. The basic requirements of the measurement are as follows:

• Concentration gradients can develop relatively quickly and persist for a long time in the system
• Chemotactic and chemokinetic activities are distinguished
• Migration of cells is free toward and away on the axis of the concentration gradient
• Detected responses are the results of active migration of cells

Despite the fact that an ideal chemotaxis assay is still not available, there are several protocols and pieces of equipment that offer good correspondence with the conditions described above. The most commonly used are summarised in the table below:

Type of assay	Agar-plate assays	Two-chamber assays	Others
Examples	PP-chamber	Boyden chamber Zigmond chamber Dunn chambers Multi-well chambers Capillary techniques	T-maze technique Opalescence technique Orientation assays

Artificial chemotactic systems

Chemical robots that use artificial chemotaxis to navigate autonomously have been designed.^[72][73] Applications include targeted delivery of drugs in the body.^[74] More recently, enzyme molecules have also shown positive chemotactic behavior in the gradient of their substrates.^[75] The thermodynamically-favorable binding of enzymes to their specific substrates is recognized as the origin of enzymatic chemotaxis.^[76] Additionally, enzymes in cascades have also shown substrate-driven chemotactic aggregation.^[77]

Apart from active enzymes, non-reacting molecules also show chemotactic behavior. This has been demonstrated by using dye molecules that move directionally in gradients of polymer solution through favorable hydrophobic interactions.^[78]

See also

• McCutcheon index
• Tropism
• Durotaxis
• Haptotaxis
• Mechanotaxis
• Plithotaxis
• Thin layers (oceanography)

References

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Further reading

Scholia has a topic profile for Chemotaxis.

• Alberts B, Johnson A, Lewis J, Walter P, Raff MC (2002). "Bacterial Chemotaxis Depends on a Two-Component Signaling Pathway Activated by Histidine-Kinase-associated Receptors". Molecular Biology of the Cell. Taylor & Francis Group.
  ISBN 978-0-8153-4069-0
  . Retrieved 18 September 2017.
• Bagorda A, Parent CA (August 2008). "Eukaryotic chemotaxis at a glance". Journal of Cell Science. 121 (Pt 16): 2621–4.
  PMID 18685153
  .
• Berg HC (1993). Random walks in biology (Expanded, rev. ed.). Princeton, NJ: Princeton Univ. Press.
  ISBN 978-0-691-00064-0
  .
• Berg HC (2003). E. coli in motion. Vol. 58. New York: Springer. pp. 64–65.
  ISBN 978-0-387-00888-2. {{cite book}}: |journal= ignored (help
  )
• Dusenbery DB (2009). Living at micro scale : the unexpected physics of being small. Cambridge, Mass.: Harvard University Press.
  ISBN 978-0-674-03116-6
  .
• Eisenbach M (2004). Lengeler JW (ed.). Chemotaxis. London: Imperial College Press.
  ISBN 978-1-86094-413-0
  .
• Eisenbach, Michael (December 2011). "Bacterial Chemotaxis". Encyclopedia of Life Sciences.
  ISBN 978-0470016176. {{cite book}}: |journal= ignored (help
  )
• Hazelbauer GL (13 October 2012). "Bacterial chemotaxis: the early years of molecular studies". Annual Review of Microbiology. 66 (1): 285–303.
  PMID 22994495
  .
• Jin T, Hereld D (2016). Chemotaxis: Methods and Protocols. Humana Press.
  ISBN 978-1-4939-3480-5
  .
• Miller LD, Russell MH, Alexandre G (2009). Diversity in bacterial chemotactic responses and niche adaptation. Vol. 66. pp. 53–75.
  PMID 19203648. {{cite book}}: |journal= ignored (help
  )
• Rao CV, Kirby JR, Arkin AP (February 2004). "Design and diversity in bacterial chemotaxis: a comparative study in Escherichia coli and Bacillus subtilis". PLOS Biology. 2 (2): E49.
  PMID 14966542
  .
• Williams AH (20 December 2010). "Chemotaxis on the move - active learning teaching tool". Journal of Microbiology & Biology Education. 11 (2): 177–8.
  PMID 23653726
  .

External links

Wikibooks has more on the topic of: Chemotaxis

Wikimedia Commons has media related to Chemotaxis.

• Chemotaxis
• Neutrophil Chemotaxis
• Cell Migration Gateway
• Downloadable Matlab chemotaxis simulator
• Bacterial Chemotaxis Interactive Simulator (web-app)