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The study of cell communication focuses on how a cell gives and receives messages with its environment and with itself. Indeed, cells do not live in isolation. Their survival depends on receiving and processing information from the outside environment, whether that information pertains to the availability of nutrients, changes in temperature, or variations in light levels. Cells can also communicate directly with one another — and change their own internal workings in response — by way of a variety of chemical and mechanical signals. In multicellular organisms, cell signaling allows for specialization of groups of cells. Multiple cell types can then join together to form tissues such as muscle, blood, and brain tissue. In single-celled organisms, signaling allows populations of cells to coordinate with one another and work like a team to accomplish tasks no single cell could carry out on its own.

The study of cell signaling touches multiple biological disciplines, such as developmental biology, neurobiology, and endocrinology. Consequently, the relevance of cell communication is quite vast, but major areas of fundamental research are often divided between the study of signals at the cell membrane and the study of signals within and between intracellular compartments. Membrane signaling involves proteins shaped into receptors embedded in the cell's membrane that biophysically connect the triggers in the external environment to the ongoing dynamic chemistry inside a cell. Signaling at the membrane also involves ion channels, which allow the direct passage of molecules between external and internal compartments of the cell. Scientists ask: What is the receptor structure that enables it to react to an external signal (such as a ligand or even a mechanical force)? Others ask: Once triggered, how is the signal processed inside the cell?

Cells have evolved a variety of signaling mechanisms to accomplish the transmission of important biological information. Some examples of this variety are receptors that allow ion currents to flow in response to photons, which effectively translates light into chemical messengers inside the cone and rod cells of the retina; growth factors that interact with the cell membrane and can trigger receptors that powerfully affect chromatin structure and the modulation of gene expression; metabolites in the blood that can trigger a cell's receptors to cause the release of a hormone needed for glucose regulation; adhesion receptors that can convey tension-generated forces that direct a cell to stay put or change direction of movement; and developmentally regulated receptors that can strictly guide the path of a migrating cell, ultimately controlling how an entire organism is wired together.

How do scientists go about studying such an intricate meshwork of interactions at the crossroads of chemistry, physics, and biology? One method is reductionist, whereby cells are isolated and cultured in vitro so that specific signals can be carefully tested with chemicals and cellular responses can be measured. Another more holistic method involves measuring cellular signaling in an intact organism (in vivo) by applying specific chemical agents that block or activate receptors in a carefully chosen tissue region and then measuring the response via an electrode that relays the activity of ion currents or via fluid sampling of the activated area. For both approaches, response measurement is vitally important, and measuring the small cellular entities is indeed a challenge. Scientists use sophisticated time-lapse microscopy to track labeled molecules that travel between subcellular compartments after a signaling event or to track the conformation of a receptor that has gone from an inactive to an active state. Furthermore, mass spectrometry techniques permit measurements of picomolar amounts, enabling the tracking of intracellular second messenger molecules that are crucial in the regulation of signals in the intracellular milieu.

Despite technical advances, global understanding of signal transduction, its internal hierarchies, and its highly integrated and extremely dynamic nature remains largely mysterious. A potential breakthrough in the field arose recently when scientists realized that there are striking analogies between signaling networks in biological systems and electronic circuits; both of them involve hierarchies, switches, modularity, redundancy, and the existence of powerful feedback mechanisms. Such a realization gave impetus to the field of computational biology as applied to cellular signaling. Today, the study of cell signaling is not restricted to biologists; with the contribution of engineers and biophysicists, scientists can now create computational algorithms that model the structure of a signaling network based on biological measurements, and these models can be used to predict the outcome of otherwise physically impossible experimental conditions. As it turns out, we are just beginning to appreciate that many of the designs and strategies we have developed to manipulate information, particularly within the digital world, are actually present in biological networks, having already been invented over the course of a hundred million years of evolution.

Image: Jorge Barrios.

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