Biomolecular gradient

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The grey represents the concentration of a molecule Cell polarity.jpg
The grey represents the concentration of a molecule

A biomolecular gradient is established by a difference in the concentration of molecules in a biological system such as individual cells, groups of cells, or an entire organism. A biomolecular gradient can exist intracellularly (within a cell) or extracellularly (between groups of cells). The purposes of such gradients in biological systems vary, but include chemotaxis and functions in development. These types of gradients play a role in many different types of signaling as well as recently being implicated in cancer metastasis.

Contents

Development

Cells themselves can create biomolecular gradients by releasing signaling molecules that diffuse outwardly. These gradients are critical for cellular identity and cell relocation. Similarly, the gradients produced by cells may influence cellular fate by their temporal and spatial characteristics. In certain organisms, the choice of cell fate can be determined by a gradient, a binary choice, or through a relay of molecules released by a cell. [1] If cell fate is binary, the identity of the cell is influenced by the presence or absence of a signaling molecule; consequently, these signals can also induce cell fate acting in a relay. [1] The relay functions by the source cell releasing a signaling molecule into the environment. Adjacent cells possessing similar cell identities respond to these signals and can release different signaling molecules to cells in their surrounding area, promoting additional new cell fates. This process continues to all cells in the developing organism. In contrast, a signal can act in a gradient, which induces a specific cell fate as a function of the concentration of the molecule in the gradient. These types of molecules are known as morphogens.

An example of this phenomenon is observed in the neural tube with varying concentrations of the Sonic Hedgehog (Shh) protein. [1] Shh is characterized as a morphogen and possesses spatial and temporal characteristics that make it well suited for study.

Cancer

Depicts migration of cells in response to types of molecules in the gradient. Chtx-AttrRep-en.png
Depicts migration of cells in response to types of molecules in the gradient.

Biomolecular gradients have been shown to facilitate the invasion of cancer cells into different types of tissues in the body. Cancer metastasis is thought to be directly coupled to growth factor gradients that facilitate chemotaxis of cancer promoter factors. These chemoattractants promote tumour angiogenesis , namely increased blood flow to tissues allowing the cancer to thrive in different areas of the body. [2] Therefore, this pathway allows for the movement of tumour-promoting molecules toward healthy tissues in the body. [2] [3] Further study is required to quantify pathways involved in the above response and may provide insight into more effective treatment for cancer patients.

Signaling

In a similar way, biomolecular gradients can function as signal antagonists that have the potential to drastically affect the cell's characteristics and in turn, the organism's response. This includes allowing the cell to distinguish its orientation or shift the barrier of cell differentiation in a group of cells. For instance, such mechanisms can be used to help the body defend against infection. Specifically, the afflicted area of the body acts as an attractant through ligand-receptor binding. This can occur through the polarity that is established by signal antagonists. In addition, this type of ligand-receptor interaction can lead to a signal cascade that trigger mitosis. A type of gradient molecule that accomplishes the aforementioned mechanism is Pom1 . [4]

Related Research Articles

<span class="mw-page-title-main">Chemotaxis</span> Movement of an organism or entity in response to a chemical stimulus

Chemotaxis is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming toward the highest concentration of food molecules, or to flee from poisons. In multicellular organisms, chemotaxis is critical to early development and development as well as in normal function and health. In addition, it has been recognized that mechanisms that allow chemotaxis in animals can be subverted during cancer metastasis. The aberrant chemotaxis of leukocytes and lymphocytes also contribute to inflammatory diseases such as atherosclerosis, asthma, and arthritis. Sub-cellular components, such as the polarity patch generated by mating yeast, may also display chemotactic behavior.

<span class="mw-page-title-main">Hormone</span> Biological signalling molecule

A hormone is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones are required for the correct development of animals, plants and fungi. Due to the broad definition of a hormone, numerous kinds of molecules can be classified as hormones. Among the substances that can be considered hormones, are eicosanoids, steroids, amino acid derivatives, protein or peptides, and gases.

Morphogenesis is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation.

<span class="mw-page-title-main">Neural tube</span> Developmental precursor to the central nervous system

In the developing chordate, 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, and ultimately the folds meet and coalesce in the middle line and convert the groove into the closed neural tube. In humans, neural tube closure usually occurs by the fourth week of pregnancy.

<span class="mw-page-title-main">Sonic hedgehog protein</span> Signaling molecule in animals

Sonic hedgehog protein (SHH) is encoded for by the SHH gene. The protein is named after the video game character Sonic the Hedgehog.

<span class="mw-page-title-main">Cell adhesion</span> Process of cell attachment

Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">Morphogen</span> Biological substance that guides development by non-uniform distribution

A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various specialized cell types within a tissue. More specifically, a morphogen is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration.

In biology, cell signaling is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes.

<span class="mw-page-title-main">Floor plate</span> Embryonic structure

The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions. It has been shown that the floor plate is conserved among vertebrates, such as zebrafish and mice, with homologous structures in invertebrates such as the fruit fly Drosophila and the nematode C. elegans. Functionally, the structure serves as an organizer to ventralize tissues in the embryo as well as to guide neuronal positioning and differentiation along the dorsoventral axis of the neural tube.

<span class="mw-page-title-main">Zona limitans intrathalamica</span>

The zona limitans intrathalamica (ZLI) is a lineage-restriction compartment and primary developmental boundary in the vertebrate forebrain that serves as a signaling center and a restrictive border between the thalamus and the prethalamus.

Decapentaplegic (Dpp) is a key morphogen involved in the development of the fruit fly Drosophila melanogaster and is the first validated secreted morphogen. It is known to be necessary for the correct patterning and development of the early Drosophila embryo and the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been suggested that Dpp plays a role in regulating the growth and size of tissues. Flies with mutations in decapentaplegic fail to form these structures correctly, hence the name. Dpp is the Drosophila homolog of the vertebrate bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily, a class of proteins that are often associated with their own specific signaling pathway. Studies of Dpp in Drosophila have led to greater understanding of the function and importance of their homologs in vertebrates like humans.

Within the field of developmental biology, one goal is to understand how a particular cell develops into a final cell type, known as fate determination. Within an embryo, several processes play out at the cellular and tissue level to create an organism. These processes include cell proliferation, differentiation, cellular movement and programmed cell death. Each cell in an embryo receives molecular signals from neighboring cells in the form of proteins, RNAs and even surface interactions. Almost all animals undergo a similar sequence of events during very early development, a conserved process known as embryogenesis. During embryogenesis, cells exist in three germ layers, and undergo gastrulation. While embryogenesis has been studied for more than a century, it was only recently that scientists discovered that a basic set of the same proteins and mRNAs are involved in embryogenesis. Evolutionary conservation is one of the reasons that model systems such as the fly, the mouse, and other organisms are used as models to study embryogenesis and developmental biology. Studying model organisms provides information relevant to other animals, including humans. While studying the different model systems, cells fate was discovered to be determined via multiple ways, two of which are by the combination of transcription factors the cells have and by the cell-cell interaction. Cells' fate determination mechanisms were categorized into three different types, autonomously specified cells, conditionally specified cells, or syncytial specified cells. Furthermore, the cells' fate was determined mainly using two types of experiments, cell ablation and transplantation. The results obtained from these experiments, helped in identifying the fate of the examined cells.

In the field of developmental biology, regional differentiation is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.

<span class="mw-page-title-main">C-C chemokine receptor type 7</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21). The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals. CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs by detecting specific chemokines, which these tissues secrete.

<span class="mw-page-title-main">French flag model</span> Biological model

The French flag model is a conceptual definition of a morphogen, described by Lewis Wolpert in the 1960s. A morphogen is defined as a signaling molecule that acts directly on cells to produce specific cellular responses dependent on morphogen concentration. During early development, morphogen gradients generate different cell types in distinct spatial order. French flag patterning is often found in combination with others: vertebrate limb development is one of the many phenotypes exhibiting French flag patterning overlapped with a complementary pattern.

<span class="mw-page-title-main">Zone of polarizing activity</span>

The zone of polarizing activity (ZPA) is an area of mesenchyme that contains signals which instruct the developing limb bud to form along the anterior/posterior axis. Limb bud is undifferentiated mesenchyme enclosed by an ectoderm covering. Eventually, the limb bud develops into bones, tendons, muscles and joints. Limb bud development relies not only on the ZPA, but also many different genes, signals, and a unique region of ectoderm called the apical ectodermal ridge (AER). Research by Saunders and Gasseling in 1948 identified the AER and its subsequent involvement in proximal distal outgrowth. Twenty years later, the same group did transplantation studies in chick limb bud and identified the ZPA. It wasn't until 1993 that Todt and Fallon showed that the AER and ZPA are dependent on each other.

<span class="mw-page-title-main">Chemotactic drug-targeting</span>

Targeted drug delivery is one of many ways researchers seek to improve drug delivery systems' overall efficacy, safety, and delivery. Within this medical field is a special reversal form of drug delivery called chemotactic drug targeting. By using chemical agents to help guide a drug carrier to a specific location within the body, this innovative approach seeks to improve precision and control during the drug delivery process, decrease the risk of toxicity, and potentially lower the required medical dosage needed. The general components of the conjugates are designed as follows: (i) carrier – regularly possessing promoter effect also on internalization into the cell; (ii) chemotactically active ligands acting on the target cells; (iii) drug to be delivered in a selective way and (iv) spacer sequence which joins drug molecule to the carrier and due to it enzyme labile moiety makes possible the intracellular compartment specific release of the drug. Careful selection of chemotactic component of the ligand not only the chemoattractant character could be expended, however, chemorepellent ligands are also valuable as they are useful to keep away cell populations degrading the conjugate containing the drug. In a larger sense, chemotactic drug-targeting has the potential to improve cancer, inflammation, and arthritis treatment by taking advantage of the difference in environment between the target site and its surroundings. Therefore, this Wikipedia article aims to provide a brief overview of chemotactic drug targeting, the principles behind the approach, possible limitations and advantages, and its application to cancer and inflammation.

Chemorepulsion is the directional movement of a cell away from a substance. Of the two directional varieties of chemotaxis, chemoattraction has been studied to a much greater extent. Only recently have the key components of the chemorepulsive pathway been elucidated. The exact mechanism is still being investigated, and its constituents are currently being explored as likely candidates for immunotherapies.

Electrotaxis, also known as galvanotaxis, is the directed motion of biological cells or organisms guided by an electric field or current. The directed motion of electrotaxis can take many forms, such as; growth, development, active swimming, and passive migration. A wide variety of biological cells can naturally sense and follow DC electric fields. Such electric fields arise naturally in biological tissues during development and healing. These and other observations have led to research into how applied electric fields can impact wound healing An increase in wound healing rate is regularly observed and this is thought to be due to the cell migration and other signaling pathways that are activated by the electric field. Additional research has been conducted into how applied electric fields impact cancer metastasis, morphogenesis, neuron guidance, motility of pathogenic bacteria, biofilm formation, and many other biological phenomena.

References

  1. 1 2 3 Harvey Lodish; Arnold Berk; S Lawrence Zipursky; Paul Matsudaira; David Baltimore; James Darnell (2008). Molecular Cell Biology. New York: W.H. Freeman and Company. ISBN   978-1-4292-0314-2.
  2. 1 2 Eccles SA (2005). "Targeting key steps in metastatic tumour progression". Curr Opin Genet Dev. 15 (1): 77–86. doi:10.1016/j.gde.2004.12.001. PMID   15661537.
  3. Keenan , Thomas M.; Albert Folch (2008). "Biomolecular gradients in cell culture systems". Lab Chip. 8 (1): 34–57. doi:10.1039/b711887b. PMC   3848882 . PMID   18094760.
  4. Moseley, J.B.; Mayeux, A.; Paoletti, A.; Nurse, P. (2009). "A spatial gradient coordinates cell size and mitotic entry in fission yeast". Nature. 459 (7248): 857–861. Bibcode:2009Natur.459..857M. doi:10.1038/nature08074. PMID   19474789. S2CID   4330336.