Cellular Communication
“Tunable interplay of self-communication and neighbor communication enables cells to span a diverse repertoire of cellular behaviors.” ~ cytologists Hyun Youk & Wendell Lim
Cells are the atoms of life. Both are organized on energetic relations.
Similarly, cellular communication is analogous to the dynamics of inorganic existence; the relations between subatomic particles, and between atoms in molecules. There is continuous interaction in all instances.
“Cell polarity is critical for the specialized function of the vast majority of cells.” ~ American molecular biologist Rong Li
Electrical potentials provide beacons of cellular organization and status. Cells construct polarity to facilitate spatial orientation within, allowing parts of a cell to understand where they are in relation to others.
To engender polarity, enzymes carefully arrange phospholipids, which are a major component of cell membranes. This alters the map of electric charges in a cell, helping shape a coherent terrain for cellular molecules to comprehend. Besides their structural role in assisting intracellular molecular orientation, phospholipids facilitate intercellular signaling.
Subatomic particles form an atom via communication. Bosons urge fermions into coherent relations. Intracellular communication functions similarly.
In organisms, biomolecules, such as proteins, are not just conglomerated atoms. They are a continuing community: in constant communication with each other.
Multicellular bodies also function as a society. Cellular actions and interrelations often follow rules of economy, just as molecular bindings and interactions adhere to their own set of energetic conventions.
Cells communicate within and without. Every cell has its own internal network. Outside is an external network: the cacophony of the neighborhood to which a cell belongs, as well as long-distance missives from conspecific cells.
Conspecific refers to the same type or species. Interspecific is of different species or varieties.
“Membrane signaling is fundamental for almost all aspects of life because that’s how information gets from outside cells to inside cells.” ~ American biochemist Adam Cohen
Elaborate sets of communication channels and protocols exist in all cells: to track events within, to procure supplies and avoid hazards from without, to fight invasion, to grow, divide, repair, to pick up on neighborhood news, and receiving marching orders to serve an organism’s greater good. Cellular communication is part of a gyre of information gathering and retention, frequently leading to decisions that initiate a new round of communication.
A cell never loses its sense of self, but its mandate is to serve its organism rather than just its own needs. Without this, eukaryotes could not develop and function, nor prokaryotes socially aggregate to greater success than individuals could ever achieve.
Cells in a multicellular organism are often not symmetrical. The cells in an animal’s intestines, for instance, need to know which side faces into the intestines, and which faces out, toward the rest of the body. This requires coordination and communication, both with neighboring cells and within, for the cell to allocate resources and process operations in the right place at the right time. Different genes are expressed in different parts of a cell to accomplish this.
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Cell signaling comprises the complex set of communication protocols that cells employ for messaging, whether within or without. In its vast diversity, cell signaling is easily one of the most intricate realms in biology.
Signal transduction defines the 2-step process of intracellular communication. 1st, an extracellular signaling molecule activates a receptor on a cell surface.
Surface reception prompts creation of another molecule, termed a 2nd messenger, which carries the signal to a target molecule within the cell; often, either in the nucleus or cytoplasm. Reception of the 2nd messenger within a cell organelle typically eventuates in a response.
Prokaryotic cellular communication is similar, though the intracellular receiver is not an organelle.
Each cell type has its own language, appropriate to its lifestyle. Cell nomenclature also includes vocabulary that is understood by other cell types, including other organisms.
The energy economics of evolution practically dictate the forms that cell signaling take, though biochemical communications have evolved context: how a specific signal is to be interpreted.
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As all eukaryotes are symbiotic, different species being able to communicate at the cellular level is essential. Consensual communications often lead to concerted actions.
In humans, commensal bacteria help keep the body in pathogen-pounding condition. Bacterial signals influence immune cell training and warn of invasion. They even fight infectious agents. The reason they do so is self-interest: invading pathogens are competition for limited resources and can wreak havoc upon the shared homestead.
Intracellular Communication
“Inside the cell, there exists a network of molecules. Between them, information is constantly being exchanged.” ~ German microbiologist Ingo Schmitz
Every cell, whether a primordial yeast or post-modern human, has a complex high-speed system of pathways for transporting cargo within, such as proteins and various vesicles. Actin cables, formed into helical filaments, are protein-paved highways. Myosin molecules are nanoscale motor proteins that ply the filaments as transporters.
A cell’s transport network is highly optimized in paths and lengths: neither too long, nor coming up short. Every cell organically finesses a fiendishly difficult geometry problem. The problem is solved by feedback: passengers communicate to the cellular machinery providing the transport via protein tokens which regulate path growth.
Transport is just one facet of cellular communication. Intracellular chat transpires in numerous ways for a wide variety of functions related to every state and stage of a cell’s life.
Using peptides (protein fragments), status updates are regularly transmitted from deep within a cell to the cell’s surface, to keep the immune system and other interested parties informed about what is going on within the cell. (Peptide-loading complexes within the endoplasmic reticulum are responsible for production and quality control of messaging peptides.) At the cell surface, MHC-1 proteins filter the data in the status updates and present only relevant information to patrolling immune system cells.
(MHC-1 is a class of immune system related glycoproteins. MHC stands for major histocompatibility complex; a term referring to biological (tissue) compatibility. There are 3 MHC classes.)
Calcium Ion Channels
Calcium ion (Ca2+) waves are a ubiquitous intracellular message medium that regulates diverse cellular activities. Besides intracellular signaling, extracellular environmental information is translated from calcium waves. The physiological correlate of cognition transpires via calcium waves traversing glia cells in the brains of animals and among plant cells. Certain proteins modulate the waves which other proteins receive and interpret.
Calcium wave communication is like music in that the intensity and frequency of waves – the distinct pattern – determines the message.
It’s like in an orchestra, where studying an isolated note on its own allows no inference of the melody. You have to hear how the frequency and volume of all instruments vary and produce the melody. Then you gain an impression of the musical piece.
“At first sight, there is no simple pattern to the ion impulses. Yet they still culminate in a meaningful response inside the cell. The pattern is the actual signal that leads to a response in the cells.” ~ Luxembourger biologist Alexander Skupin
Electrons
“Electrons are the fuel.” ~ Chinese molecular biologist Chang-Jun Liu
Calcium ion waves illustrate the modus operandi of communication at the most basic physical level: the deliberate movement of electrons.
Proteins specify construction of cellular materials by precisely placing electrons. For instance, plant cell proteins selectively allocate electrons at just the right time to produce the specific type of lignin that a plant wants. Lignin is the complex polymer that provides the scaffolding for algae and plant cells.
Salmonella bacteria are intracellular pathogens. They ply their infectious trade by shuffling electrons.
To spread their infection, Salmonella hitch rides in macrophages, which are immune system cells responsible for containing infection. First, a bacterium calls for a taxi by generating an electric field which attracts white blood cells. Macrophages engulf the electrified Salmonella, supposedly succeeding in pathogen containment.
Once ensconced in a while blood cell, a Salmonella changes its electronic songs to get the macrophage to leave the intestinal tissue where the cell made its capture. The macrophage enters the circulatory system carrying its captive. The Salmonella then entices its release with an electronic signal, thus allowing the infection to spread through the body. A wily symphony of electrons has macrophages dancing like puppets to Salmonella’s tune.
Prokaryote Palindromes
To protect themselves against chemical threats, many prokaryotes, including bacteria and archaea, employ a toxin-antitoxin (TA) system. A TA system is a set of 2 or more linked genes which together encode for both a toxin protein and a corresponding antitoxin. A TA system allows for recognition (of a toxin) and remedy (by applying the antitoxin).
There are 6 known toxin-antitoxin systems, which are classified by the physical medium the antitoxin uses to neutralize the toxin. RNA is used in types 1 and 3. The type 2 system inhibits a toxic protein by binding an antitoxin protein to it, imprisoning the toxin. Types 4–6 are less common than the first 3.
Bacteria are fond of type 2 TA. The genetic information to implement this system can be tucked into a plasmid (a tiny capsule) and shared with others – horizontal gene transfer. This helps bacterial colonies survive what would otherwise be a lethal onslaught.
A palindrome is a word that reads the same forward or backward. Civic is an exemplary palindrome.
In over 25% of known bacteria species, the instructions that tell type 2 antitoxin proteins how to do their job are encoded as palindromes. Archaea also use TA palindromes.
The especial advantage of palindromes is robustness. A portion of a palindrome may be damaged yet still be decipherable by knowing that the message is a palindrome. The coherence behind evolution can be quite the clever packager.
Intercellular Communication
“All cells use information about the forces in their environments to direct decisions about migration, division, and cell fate.” ~ American cytologist Douglas Robinson
Cells live by intelligence. This requires interactive communication.
There are ~200 different cell types in the 37.2 trillion cells in a human body. Most cells express dozens, or even hundreds, of distinct cell messenger molecules (ligands) and receptors – creating a highly-interconnected network of cell types which intercommunicate through multiple ligand-receptor pathways.
Cells speak only a handful of different molecular languages to work together to carry out an incredible diversity of tasks. These languages are sophisticated and have a large vocabulary. ~ American biologist Michael Elowitz
As a plant grows, each cell needs to know its place in relation to other cells. Cells communicate to create the patterns from which different tissues arise. Plants do so using small bits of RNA, which is a particularly rich information medium.
Unlike conventional development signals, small RNAs operate in a highly specific way, and they can intervene directly in gene activity. ~ German plant geneticist Marja Timmermans
Besides monitoring internal operations, cells constantly acquire information about their external environment. This information is critical to making informed decisions about processes essential to survival, growth, and reproduction.
Age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization.
~ American cytologist Martin Hetzer et al
Organs and cells comprise constituent components at different ages. Every organ is a mix of old and new cells. Every cell has novice and experienced proteins. The reason is educational: for youngsters to learn from their elders how the show is run.
Sweet Talk
“Telltale surface sugars enable cells to identify and interact with one another.” ~ Israeli biochemists Nathan Sharon & Halina Lis
All cells wear a coat of sugar molecules (glycans) as part of surface glycoproteins. Glycans stick out like an antennae forest. Glycans can cluster and thereby channel water over a surprisingly large range: tens of nanometers (a water molecule is a mere 0.3 nm). By this, sugar facilitates communication through intercellular fluid.
Stem Cell Conference
Stem cells are the mother of all eukaryotic cells: generics that can differentiate into specialized cells to perform specific functions. Stem cells can also self-renew and generate more stem cells.
Early in an organism’s life, following a development plan, embryonic stem cells differentiate into cells that form various tissues and organs. This process comes from exquisitely coordinated dialogues between cells. At least 3 different protein networks are involved in stem cell differentiation.
1st, activating and deactivating various genes direct a stem cell toward differentiation. This involves a flurry of epigenetic intracellular communication.
2nd, epigenetic tags on messenger RNA of activated genes properly nudge a cell toward differentiation.
3rd, the feedback loop that normally inhibits cell proliferation is blocked, allowing rapid cellular development in the determined direction. Cancer cells proliferate by blocking this inhibiting feedback loop.
Epigenetics provides both the language and recordkeeping of what is going on during this complex conference, which eventuates in a stem cell taking on a new role.
As needed throughout life, stem cells provide repairs by replacing damaged cells. The communication process involved is selfsame to that during development.
Wounds
“Epithelial wound healing is a multistage process. Cells must detect the presence of a wound, migrate and proliferate in a coordinated fashion to close the defect, and then successfully reestablish tissue-wide epithelial architecture.” ~ American cytologist Erica Shannon et al
One way that damaged and dying animal cells communicate their distress is by releasing specific proteins into the extracellular fluid. Another way is through specialized intercellular tactile connections. These junctions allow neighbors to directly exchange electrical impulses, ions, and molecules.
Other cells pick up on these signals and boost their internal calcium levels, triggering a transformation from static to mobile form, allowing undamaged cells to initiate wound repair.
Communal Encyclopedia
“Biological production of extracellular vesicles is widespread, with vesicles produced by species across all branches of the tree of life.” ~ English marine microbiologist David Scanlan
Cells in all domains of life produce membraned vesicles (MVs) that contain lipids, proteins, and genic information. These vesicles are constantly secreted into the surrounding environment. MV production and secretion is dynamic and manipulatable, allowing cells to send informational messages and receive feedback.
Exosomes are saucer shaped MVs produced by most eukaryotic cells. All kinds of cells, including cancer cells, communicate over long distances using exosomes.
By their ubiquity, MVs provide a communal encyclopedia. Cells selectively incorporate encountered vesicles to ascertain a wealth of information about the neighborhood in which they live and its history.
This knowledge is especially helpful to microbes, which often traverse new territory. The genetic data in vesicles is especially useful as it affords transfer of nifty adaptations which may be incorporated and employed accordingly.
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Cells constantly adjust their metabolism based upon available nutrients. They regulate their repairs and transitions through the cell life cycle based upon accessible supplies, requisitioning specific compounds through the cellular communication network as needed.
In a multicellular context, individual cells transform, reproduce, or even commit programmed suicide (apoptosis), to benefit the survival prospects of the whole organism. Dying cells interact with their neighbors, apprising them of their situation. They can send signals for other cells to proliferate and tell cells from afar that it is time for them to die too.
During development, certain cells must surrender their lives to advance an organism to the next stage. Fingers emerge from paddle-shaped hands by apoptosis of the cells that form the webbing between digits-to-be. Such self-sacrifice is the ultimate expression of intercellular cooperation.
“Cell-to-cell communication plays critical roles in specifying cell fate and coordinating development in all multicellular organisms.” ~ Chinese molecular biologist Xianfeng Morgan Xu
Primary Cilia
A cilium is a slender protuberance projecting from a eukaryotic cell body. There are 2 types of cilia: motile and primary (non-motile).
Motile cilia are like the flagella on bacteria and some eukaryotic cells: a means of moving about. Sperm cells have motile cilium that lets them swim to their target and consummate a love connection.
A bacterium’s flagellum is a single lash-like tail that propels a bacterium through a fluid. A bacterium also uses its flagellum as a sensory organelle. Some bacteria, like Helicobacter pylori, which lives in the stomach, have multiple flagella.
Primary cilia are found in most animal cells. They were discovered in 1867 by Russian biologist Alexander Kovalevsky. Quickly dismissed as an evolutionary artifact of no significance, primary cilia were ignored for over a century.
The primary cilium is a cell’s transceiver: detecting a wealth of information about its surroundings and acting as a cell status transmitter. The primary cilium picks up protein-based chemical signals and information from mechanical forces, such as fluid flow and tensile force, in the immediate vicinity.
Cell status sent via primary cilium is essential to development and tissue maintenance, allowing coordination that otherwise would not happen. Primary cilia help orient stem cells in their direction of growth. Diseases result if primary cell cilia are not working properly.
For efficiency, there is only 1 primary cilium per cell. Multiple cilia would degrade signal reception quality as well as increase cellular complexity without advantage.
Communication Lines
Cells constantly communicate with each other by direct contact (juxtacrine signaling), over short distances (paracrine signaling), and long distances (endocrine signaling).
Direct communication between adjacent cells underlies tissue organization. Contact signals use a simple sugar (oligosaccharide), protein, or lipid component of the cell membrane to message.
Nerve cells are juxtacrine signalers: translating internal electric pulses into chemical communiqués that are passed cell-to-cell over gap junctions. These conversations are overheard by nearby cells.
Brain stem cells monitor activity, listening in on nearby nerve and glia cells. This chemical eavesdropping regulates new cell growth.
Paracrine signals are used for cell growth and repair, including blood clotting and scar tissue formation. Allergen responses are initiated by paracrine signals.
Insects and crustaceans control growth through paracrine signals: allatostatins, which are neuropeptide hormones. Retinoic acid, the active form of vitamin A, is an allatostatin which regulates gene expression during embryonic development in higher animals.
Short-distance statements are typically designed to degrade quickly, as diffusion could lead to disruption rather than appropriate action.
Long-distance communication is big business in a multicellular organism; the medium to living large.
Neurons communicate over long distances via long fibers – axons – that send electrical signals. These cells provide the intelligence network known as the nervous system.
Other cells have cellular extensions – filopodia – which are used for sensing, cell-to-cell interactions, and migration. Cytonemes are long, thin filipodia that are specialized for exchanging signaling proteins between cells over long distances. Filopodia form a dedicated network by directly extending from cells that receive signaling proteins to cells that make them. Physical connection between cytonemes completes a private communication channel between cells.
The endocrine system is the glandular network. Glands produce hormones that traverse the bloodstream with regulation instructions.
Hormone is a general term for any endocrine signaling compound. All multicellular organisms produce hormones. Plant hormones are termed phytohormones. Animals typically transport hormones in the blood.
A hormone hits home on a certain cell receptor by binding to its receptor protein. This reception is then translated into cell-speak by a 2nd messenger. The cell then decides on an internal response.
In contrast to the glands of the endocrine system, exocrine glands are doers, not talkers: secreting their products exclusively through dedicated ducts directly into the external environment. Saliva, sweat, mucus, and mammary are mammal exocrine glands.
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Killer Diagrams
All animals have protection against the pathogens to which they are susceptible via an innate immune system.
Evolution upped the defensive game for vertebrates, which have an adaptive immune system that can learn and remember attacks to better cope the next time around. Innate immune systems also possess some memory, but it is not as sophisticated as in the adaptive variety.
Taking out the opposition is a team sport. Different cell classes and types are tasked with different roles and responsibilities.
For instance, there are 4 functional types of T cells, which play different roles: hunting (killers), assisting (helpers), not overdoing it (regulators), and archiving the episode (historians).
Killer T’s hunt in small packs. They converse as they prowl, expressing themselves by placing specific proteins on their surfaces.
T talk is tactile. T cells rub up against one another, placing new proteins into the interface between them. These protein paintings are organized into beautiful patterns. One looks like a bullseye. The spacing of the patterns is significant, as is the rigidity of the cell surface on which painting is done. T cells indulge in artful con-versation before terminating pathogens with extreme prejudice.
Cancer Cells
Cells must sense extracellular signals and transfer the information contained about their environment reliably to make appropriate decisions. ~ English biologist Margaritis Voliotis et al
Cell sickness is characterized by a cell dropping social communication; leaving various feedback loops unanswered. Cancer cells arise this way: following their own inner voice while ignoring orders to cease and desist. Then, as a cellular sociopath, cancer turns intercellular communication to its own ends.
Cancer starts in one tissue before it spreads to certain types of secondary tissue. The mystery of metastasis lies in communication. Cancer cells decide secondary infection by trying to start a conversation with new tissues. Those that answer are invaded. By this, breast cancer makes its way into bone.
