Organized Activity
Form and function in cytology are simply different perspectives, as the two are inexorably intertwined. In this, the precepts of physics and chemistry provide the foundation for life. That withstanding, living is a matter of intelligently applying energy.
Communication
There is a constant flurry of communication and coordination in every cell. Chemical messages flit back and forth.
Cells maintain their integrity and reproduce via genetic material. Operationally, a cell’s genome is a massive instruction manual for producing proteins and other bioproducts. This manual expresses the language of life via coordinated conferencing.
Though the functions of prokaryotes and eukaryotes are comparable, the elaborate structure of even a single eukaryotic cell means that its communication needs are inherently more complex than those of a prokaryote.
Extracellular Matrix
The complexity of eukaryotes is massively multiplied with multicellularity. Most cells in a multicellular organism are in close, ongoing associations with their neighbors.
Tissues are cell masses joined by junctions, or by an extracellular matrix (ECM) of secreted glycosylated (carbohydrate-rich) proteins that create attachment bases for cells: holding tissue together without direct contact between neighboring cells.
Glycocalyx is a common glycoprotein ECM, produced by some bacteria as well as eukaryotic cells. Glycolcalyx forms a coating on the outside surface of a cell membrane. The slime on the outside of a fish is a glycolcalyx.
Glycocalyx plays various roles: cell recognition, cell adhesion, protection, and acting as a permeability barrier. Glycocalyx acts as one way for an organism to distinguish between its own healthy cells and those that are diseased, as well as assisting in recognizing invaders. Multicellular organisms expend tremendous time and energy building and maintaining molecular forests of glycocalyx.
ECM glycoproteins come in various shapes and sizes, but functionally they fall into 3 groups: transporters, ion channels, and receptors.
Transporters carry specific molecules, usually food, across cell membranes. Each type of molecule has its own jitney model.
Ion channels are gated communication pathways that form a selective signaling matrix. Communications across cell membranes are regulated by ion channels.
Receptors are the most diverse group of cell-surface glycoproteins. Each receptor is designed to respond to a specific signaling molecule. A signaling molecule binding to its receptor sets off a sequence of biochemical events which may regulate cell production, growth, or even death (apoptosis).
The various communications systems of multicellular organisms, such as the nervous and endocrine systems, are multifaceted matrices that use ECMs.
Movement
For a cell to move forward it must convert chemical energy into mechanical propulsion. ~ Swedish engineer Pontus Nordenfelt et al
The great advantage of multicellular organisms is specialization: differentiated cells that perform different tasks. Specialization requires coordination. Coordination involves movement; well, sometimes. Plant cells are immobile. The genetic and hormonal networks that control plant growth are completely different than for metazoa with their motile cells. (A metazoan is a multicellular animal.)
Chemotaxis is cellular movement toward or away from a chemical stimulus. Among other uses, chemotaxis lets stem cells find, and reside in, proper locations.
During embryonic development (embryogenesis), chemotaxis is repeatedly employed to rearrange cells. This occurs during primordial germ cell migration, organ formation, and wiring the nervous system.
Embryogenesis involves undifferentiated cells arranging themselves into groups of functionally similar cells to form tissues. Developing embryos are awash in signals that guide cells and spur cell differentiation, thus forming organs.
An individual in a collective consciously tries to align its movements with those of its neighbors, which involves orchestrated sensing and action. So it is with the collective migration of cells. ~ German cytologist Joachim Spatz
Many cells are migrant workers. Red blood cells flow to deliver oxygen. White blood cells roam the circulatory system. When one encounters a wound, it releases epidermal growth factor, a chemical transmission which summons other white blood cells to assist.
Healing
In recovering from a wound, new cells must locomote to the right location. To move into place, part of the cytoplasm temporarily rigidifies, affording a fluid creeping motion by stretching and retraction of the right parts at the right time – an elaborately coordinated exercise.
In an adult, chemotaxis mediates the trafficking of immune cells, and is crucial for inflammation. Chemotaxis also participates in wound healing, and in tissue maintenance.
Cells use slight differentials of molecular concentrations in fluid to tell which direction they should go.
Cells can detect differences in concentration as low as 2%. They’re also versatile: detecting small differences whether the background concentration is very high, very low or somewhere in between. ~ American cytologist Peter Devreotes
Detecting gradients is a 2-step process. First, a cell tunes out background noise. Next, the side of the cell getting less of the chemical signal stops responding to it.
Then, the control center inside the cell ramps up its response to the message it’s getting from the other side of the cell and starts the cell moving toward that signal. ~ Chinese cytologist Chuan-Hsiang Huang
As cells migrate, they transmit mechanical forces from their leading edge, creating a stress wave that propagates through tissue. This stress gradient creates a faint electrical field that is detectable by nearby cells.
These forces are generated backward, from cell to cell, through intercellular junctions. This build-up of stress gradients and voltage guides cells in the right direction.
Meanwhile, cell fragments move in the opposite direction of the electrical charge. Thus, wounded tissue is more easily cleared as replacements arrive.
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Cells are not just sacks of jelly. They have a complex structure which includes scaffolding: a network of wiry molecules that maintain cell integrity, as well as microtubular piping acting as intracellular conduits for data transmission.
Around the edges of cells are networks of filaments. These filaments, composed of actin, are in constant flux, even when a cell is not moving.
For a vast variety of purposes, cells migrate collectively via intermittent bursts of activity. That takes planning.
Cells talk to nearby cells and compare notes before they make a move. ~ Russian American biophysicist Ilya Nemenman
A cell moves by converting chemical energy into mechanical force. 3 molecule families work together to enable cell migration: actins, integrins, and cadherins.
Actin is a family of proteins on the inside of the cell membrane which collectively form a cell’s skeleton, and so help maintain cell shape as well as effect cell motility. Actin participates in many other cell processes, including communication, cell division (mitosis), and organelle organization.
Integrins are transmembrane receptor molecules on the cell surface that can attach themselves to other surfaces. Integrins act as communication bridges for cell-to-cell and cell-extracellular matrix interactions.
There are several types of integrins. They work alongside other cell receptors, including cadherins.
An adapter protein links actin and integrin together to effect cell movement.
Once the adaptor has connected the integrins and actin, the mechanical force from actin gives the ‘green light.’ The integrin molecule then binds itself to a nearby partner surface, through which the cell can move slightly forward.
Once the cell’s migration is complete, the integrin and actin molecules separate from each other in this part of the cell, while another part of the cell becomes active. ~ Pontus Nordenfelt
Cell migration is governed by integrin molecules, which coordinate to become active in the necessary regions to propel movement in the intended direction. But the general mechanism for locomotion involves localized actin polymerization.
A cell moves by building filaments in the direction of movement, while tearing down filaments on the tail end. As this happens, the cell surfaces bulges, forming a lobe, and then uses molecular clamps to grab onto the underlying surface.
A cell swims and tugs its way. It is an intricate dance that takes a lot of energy.
Of course, a cell needs to know which way to go. Multiple cells often form a train, migrating as a group.
Cadherins are a class of cell membrane proteins. The term derives from “calcium-dependent adhesion,” as cadherins operate via calcium ions (Ca2+): a common cellular modus operandi.
Cadherins were long thought to merely act like mortar between bricks: holding cells together and preventing motility. But cadherins are not just glue.
Cadherin is serving multiple purposes, all of which function together to coordinate the collective ability of these cells to sense direction. ~ American cytologist Denise Montell
Each of the different cadherins cluster together with others of their kind. Cadherins on one cell create a zipper-like connection with others on another cell.
Cells recognize one another and coordinate cell migration via cadherins and other cell adhesion molecules (CAMs) – tethering cells together and pulling them in the proper direction.
Cells can sense not just the precise concentration of a chemical signal, but concentration differences. That’s very important because in order to know which direction to move, a cell has to know in which direction the concentration of the chemical signal is higher. Cells sense this gradient and it gives them a reference for the direction in which to move and grow. ~ Ilya Nemenman
Another class of CAM provides adhesion without relying upon calcium. Some of these cell adhesion proteins are involved in forming nerve cell contacts and neural grouping.
When cells from 2 different tissues are dissociated mechanically, or by treatment with enzymes and then mixed in a culture medium, the cells re-aggregate into different groups according to their origin. The cell adhesion molecules on the cell surface provide markers identifying the different cells.
Cancer cells metastasize (spread) by altering CAM function to lose cell adhesion. Conversely, many pathogens and parasites use CAM proteins as signposts, and to colonize by binding firmly to mucosal surfaces.
Cells move differently, depending upon their situation within tissues: alternately using adhesive or electrostatic forces to propel themselves. To avoid detection, cancer cells mimic the way native cells move.
If cancer is to spread from one part of the body to another, it will encounter a diverse range of tissue environments. Being able to switch movements is the most important factor in making a cancer cell dangerous. ~ English pathologist Erik Sahai
A transmember protein can travel through a cell membrane. Many transmember proteins act as border guards at membranes, denying or allowing specific molecules, either in or out. Transmembrane proteins recognize their clientele. They ferry some molecules across by particularly folding or bending to move the molecule through.
Push & Shove
Force induces additional interactions at the atomic scale. Residues that had previously not been making contact are now interacting. These are force-induced interactions. ~ Chinese microbiologist Cheng Zhu
Much cell activity is lively chemistry. But jostling about is also important. Mechanical forces can regulate cellular chemical reactions and cell functions. Tensile pressures are applied to cells all the time.
A cell might rearrange its cytoskeleton to accommodate an applied force, or apply its own forces to do something, such as moving itself. Cells can vary their mechanical environment to affect their biochemical environment.
Self-Organization
Recognition of changing conditions is essential for proper cellular activity. The most sensitive possible perception would be for a cell to keep itself close to the edge of self-organized criticality. That is in fact how biology operates, from the macromolecular to the cellular level. Biochemical interaction networks form an operational state memory in multiple dimensions, provide the means for self-assembly for complex functioning, and facilitate organizational dissolution when a structure is no longer needed.
Successful development of multicellular animals requires cooperative intercellular interactions and coordination that ensure tissue integrity. Various mechanisms enforce these behaviors.
One such mechanism monitors genetic identity, preventing uncooperative cells from contributing. How genetic disparities are recognized is unknown but determining cell fitness via co-acting communications is a critical component.
Cells within developing tissues that are recognized as mutant or compromised are competitively eliminated. ~ Swiss molecular biologist S.N. Meyer et al
Phase transitions are used to spatially organize and regulate cellular information storage and transfer. A small change triggering a single transition point can create a large response through cascading effect. An example of this butterfly effect is in phase transitions which organize cellular compartments.
Cells have numerous examples of nonmembrane-bound compartments containing many proteins that perform complex biochemistry. These compartments form rapidly and are disassembled when not required. ~ Finnish biochemist Kai Simons & English cytologist Anthony Hyman
