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Cell–cell interaction refers to the direct interactions between cell surfaces that play a crucial role in the
development Development or developing may refer to: Arts *Development (music), the process by which thematic material is reshaped * Photographic development *Filmmaking, development phase, including finance and budgeting * Development hell, when a proje ...
and function of
multicellular A multicellular organism is an organism that consists of more than one cell (biology), cell, unlike unicellular organisms. All species of animals, Embryophyte, land plants and most fungi are multicellular, as are many algae, whereas a few organism ...
organisms. These interactions allow cells to communicate with each other in response to changes in their microenvironment. This ability to send and receive signals is essential for the survival of the cell. Interactions between cells can be stable such as those made through cell junctions. These junctions are involved in the communication and organization of cells within a particular tissue. Others are transient or temporary such as those between cells of the
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
or the interactions involved in tissue
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. These types of intercellular interactions are distinguished from other types such as those between cells and the
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 ...
. The loss of communication between cells can result in uncontrollable cell growth and
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
.


Stable interactions

Stable cell-cell interactions are required for
cell adhesion 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_junction, cell junc ...
within a tissue and controlling the shape and function of cells. These stable interactions involve
cell junction Cell junctions or junctional complexes are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring Cell (biology), cells or between a cell and the extracellular matrix in animals. Th ...
s which are multiprotein complexes that provide contact between neighboring cells. Cell junctions allow for the preservation and proper functioning of epithelial cell sheets. These junctions are also important in the organization of tissues where cells of one type can only adhere to cells of the same tissue rather than to a different tissue.


Tight junctions

Tight junctions are multi-protein complexes that hold cells of a same tissue together and prevent movement of water and water-soluble molecules between cells. In epithelial cells, they function also to separate the extracellular fluid surrounding their apical and basolateral membranes. These junctions exist as a continuous band located just below the apical surface between the membranes of neighboring epithelial cells. The tight junctions on adjacent cells line up so as to produce a seal between different tissues and body cavities. For example, the apical surface of gastrointestinal epithelial cells serve as a selective permeable barrier that separates the external environment from the body. The permeability of these junctions is dependent on a variety of factors including protein makeup of that junction, tissue type and signaling from the cells. Tight junctions are made up of many different proteins. The four main transmembrane proteins are occludin, claudin, junctional adhesion molecules (JAMs) and tricellulins. The extracellular domains of these proteins form the tight junction barrier by making homophilic (between proteins of the same kind) and heterophilic interactions (between different types of proteins) with the protein domains on adjacent cells. Their cytoplasmic domains interact with the cell cytoskeleton to anchor them.


Anchoring junctions

Of the three types of anchoring junctions, only two are involved in cell-cell interactions: adherens junctions and desmosomes. Both are found in many types of cells. Adjacent epithelial cells are connected by adherens junctions on their lateral membranes. They are located just below tight junctions. Their function is to give shape and tension to cells and tissues and they are also the site of cell-cell signaling. Adherens junctions are made of cell adhesion molecules from the
cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...
family. There are over 100 types of cadherins, corresponding to the many different types of cells and tissues with varying anchoring needs. The most common are E-, N- and P-cadherins. In the adherens junctions of epithelial cells,
E-cadherin Cadherin-1 or Epithelial cadherin (E-cadherin), is a protein that in humans is encoded by the ''CDH1'' gene (not to be confused with the APC/C activator protein CDH1). Mutations are correlated with Hereditary diffuse gastric cancer, gastric, Here ...
is the most abundant. Desmosomes also provide strength and durability to cells and tissues and are located just below adherens junctions. They are sites of adhesion and do not encircle the cell. They are made of two specialized cadherins,
desmoglein The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another. Pathology Desmogleins are targeted in the autoimmune disease ...
and desmocollin. These proteins have extracellular domains that interact with each other on adjacent cells. On the cytoplasmic side, plakins form plaques which anchor the desmosomes to intermediate filaments composed of keratin proteins. Desmosomes also play a role in cell-cell signaling.


Gap junctions

Gap junctions Gap junctions are Membrane channel, membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such small molecules, substrates, and metabolites. Gap junctions were first described as ''close appositions' ...
are the main site of cell-cell signaling or communication that allow small molecules to diffuse between adjacent cells. In
vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
, gap junctions are composed of transmembrane proteins called
connexin Connexins (Cx)TC# 1.A.24, or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, forms gap junctions in invertebrates. Eac ...
s. They form hexagonal pores or channels through which ions, sugars, and other small molecules can pass. Each pore is made of 12 connexin molecules; 6 form a hemichannel on one cell membrane and interact with a hemichannel on an adjacent cell membrane. The permeability of these junctions is regulated by many factors including pH and Ca2+ concentration.


Receptor proteins in direct-contact signaling

Receptor proteins on the cell surface have the ability to bind specific signaling molecules secreted by other cells.
Cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
allows cells to communicate with adjacent cells, nearby cells (
paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...
) and even distant cells (
endocrine The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...
). This binding induces a conformational change in the receptor which, in turn, elicits a response in the corresponding cell. These responses include changes in gene expression and alterations in
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
structure. The extracellular face of the plasma membrane has a variety of
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
,
carbohydrates A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ma ...
, and
lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...
which project outward and act as signals. Direct contact between cells allows the receptors on one cell to bind the small molecules attached to the plasma membrane of different cell. In eukaryotes, many of the cells during early
development Development or developing may refer to: Arts *Development (music), the process by which thematic material is reshaped * Photographic development *Filmmaking, development phase, including finance and budgeting * Development hell, when a proje ...
communicate through direct contact. Synaptic signaling, an integral part of
nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
activity, occurs between
neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
and target cells. These target cells can also be neurons or other cell types (i.e.
muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
or
gland A gland is a Cell (biology), cell or an Organ (biology), organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also funct ...
cells). Protocadherins, a member of the
cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...
family, mediate the adhesion of neurons to their target cells at
synapses In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
otherwise known as synaptic junctions. In order to for communication to occur between a neuron and its target cell, a wave of depolarization travels the length of the neuron and causes neurotransmitters to be released into the synaptic junction. These neurotransmitters bind and activate receptors on the post-synaptic neuron thereby transmitting the signal to the target cell. Thus, a post-synaptic membrane belongs to the membrane receiving the signal, while a pre-synaptic membrane is the source of the neurotransmitter. In a
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...
, a synapse is formed between a
motor neuron A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly o ...
and muscle fibers. In
vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
,
acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
released from the motor neuron acts as a neurotransmitter which depolarizes the muscle fiber and causes
muscle contraction Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in musc ...
. A neuron's ability to receive and integrate simultaneous signals from the environment and other neurons allows for complex
animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
behavior Behavior (American English) or behaviour (British English) is the range of actions of Individual, individuals, organisms, systems or Artificial intelligence, artificial entities in some environment. These systems can include other systems or or ...
.


Plant cell-cell interactions

Plant cells Plant cells are the cells present in green plants, photosynthetic eukaryotes of the kingdom Plantae. Their distinctive features include primary cell walls containing cellulose, hemicelluloses and pectin, the presence of plastids with the capab ...
are surrounded by cell walls which are barriers for cell-cell communication. This barrier is overcome by specialized junctions called
plasmodesmata Plasmodesmata (singular: plasmodesma) are microscopic channels which traverse the cell walls of plant cells and some algal cells, enabling transport and communication between them. Plasmodesmata evolved independently in several lineages, and spe ...
. They are similar to gap junctions, connecting the cytosol of adjacent cells. Small molecules (<1000 Da), such as ions, amino acids, and sugars, can diffuse freely through plasmodesmata. These small molecules include
signaling molecule In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
and
transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...
. The size of the channel is also regulated to allow molecules up to 10,000 Da in size. The permeability of these channels is dependent on many factors, including Ca2+ concentration. An increase in cytosolic Ca2+ concentration will reversibly limit passage through the plasmodesmata. Unlike gap junctions, the cell membranes of adjacent cells merge to form a continuous channel called an annulus. Additionally, within the channel, there is an extension of the
endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
, called a desmotubule, which spans between the cells. The cell-cell interactions facilitated by plasmodesmata play an important role in development of plant cells and tissues and defense against viral infection.


Transient interactions


Immune system

Leukocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
or white blood cells destroy abnormal cells and also provide protection against bacteria and other foreign matter. These interactions are transitory in nature but are crucial as an immediate immune response. To fight infection, leukocytes must move from the blood into the affected tissues. This movement into tissues is called extravasation. It requires successive forming and breaking of cell-cell interactions between the leukocytes and the endothelial cells that line blood vessels. These cell-cell interactions are mediated mainly by a group of
Cell Adhesion Molecules Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
(CAMs) called selectins. T helper cells, central to the immune system, interact with other leukocytes by releasing signals known as
cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
which activate and stimulate the proliferation of
B cells B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
and killer T cells. T helper cells also directly interact with
macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
, cells that engulf foreign matter and display
antigens In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. An ...
on its surface. T-helper cells that possess the appropriate receptors can bind to these antigens and proliferate resulting in T-helper cells that have the ability to identify the same antigens.


Coagulation

Coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
or blood clotting relies on, in addition to the production of
fibrin Fibrin (also called Factor Ia) is a fibrous protein, fibrous, non-globular protein involved in the Coagulation, clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerization, polymerize. ...
, interactions between
platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...
. When the
endothelium The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
or the lining of a blood vessel is damaged,
connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
including
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
fibers is locally exposed. Initially, platelets stick to the exposed connective tissue through specific cell-surface receptors. This is followed by platelet activation and aggregation in which platelets become firmly attached and release chemicals that recruit neighboring platelets to the site of vascular injury. A meshwork of fibrin then forms around this aggregation of platelets to increase the strength of the clot.


Cell interactions between bacteria

Bacterial populations interact in a similar manner to cells in tissue. They communicate through physical interactions and signaling molecules such as homoserine lactones and peptides as a means to control metabolism and regulate growth . A common example and one of the most studied forms of bacterial cell interactions is biofilm.
Biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...
is a cell aggregate that can be attached to biological or abiotic surfaces. Bacteria form biofilms to adapt to various environments such as changes in substrate availability. For example, the formation of biofilm increases a bacterial cell's resistance to antibiotics compared to cells which are not part of the aggregate.


Pathological implications


Cancer

Cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
can result from the loss of cell-cell interaction. In normal cells, growth is controlled by contact inhibition in which contact with neighboring cells causes a stunt in cell growth. Contact inhibition is thought to be mediated by
cadherin Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...
s, proteins that play an important role in
cell adhesion 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_junction, cell junc ...
. This inhibition prevents cells from piling up on top of one another and forming mounds. However, in cancerous cells where expression of E-cadherin is lost, contact inhibition is lost and results in uncontrolled growth or proliferation, tumor formation, and
metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
.


Bacterial pathogens

In order for
pathogenic bacteria Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are Probiotic, beneficial but others can cause infectious diseases. The nu ...
to invade a cell, communication with the host cell is required. The first step for invading bacteria is usually adhesion to host cells. Strong anchoring, a characteristic that determines virulence, prevents the bacteria from being washed away before
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
occurs. Bacterial cells can bind to many host cell surface structures such as glycolipids and glycoproteins which serve as attachment receptors. Once attached, the bacteria begin to interact with the host to disrupt its normal functioning and disrupt or rearrange its cytoskeleton. Proteins on the bacteria surface can interact with protein receptors on the host thereby affecting signal transduction within the cell. Alterations to signaling are favorable to bacteria because these alterations provide conditions under which the pathogen can invade. Many pathogens have Type III secretion systems which can directly inject protein toxins into the host cells. These toxins ultimately lead to rearrangement of the cytoskeleton and entry of the bacteria.


Disease

Cell–cell interactions are highly specific and are tightly regulated. Genetic defects and dysregulation of these interactions can cause many different diseases. Dysregulation that leads to leukocyte migration into healthy tissues can cause conditions such as
acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin co ...
and some types of arthritis. The autoimmune disease
pemphigus vulgaris Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. Pemphigus was derived from the Greek word ''pemphix'', meaning blister. It is classified as a type II hypersensitivity reaction in which antibody, ...
results from
autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...
to
desmoglein The desmogleins are a family of desmosomal cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another. Pathology Desmogleins are targeted in the autoimmune disease ...
and other normal body proteins. The autoantibodies disrupt the adhesion between epithelial cells. This causes blisters of the skin and mucous membranes. Mutations in the connexin genes cause 8 human diseases including heart malformations and neurosensory deafness.


References

{{DEFAULTSORT:Cell-cell interaction Cell biology Cell communication Cell signaling Molecular biology