How we sense the world has, ultimately, a cellular and molecular basis. We have these big brains that do amazingly sophisticated processing to interpret the flood of sensory information pouring in through our eyes, our skin, our ears, our noses…but when it gets right down to it, the proximate cause is the arrival of some chemical or mechanical or energetic stimulus at a cell, which then transforms the impact of the external world into ionic and electrical and chemical changes. This is a process called sensory signaling, or sensory signal transduction.

While we have multiple sensory modalities, with thousands of different specificities, many of them have a common core. We detect both light and odor (and our cells also sense neurotransmitters) with similar proteins: they use a family of G-protein-linked receptors. What that means is that the sensory stimulus is received by a receptor molecule specific for that stimulus, which then actives a G-protein on the intracellular side of the cell membrane, which in turn activates an effector enzyme that modifies the concentration of second messenger molecules in the cell. Receptors vary—you have a different receptor for each molecule you can smell. The effector enzymes vary—it can be adenylate cyclase, which changes the levels of cyclic AMP, or it can be phospholipase C, which generates other signalling molecules, DAG and IP₃. The G-protein that links receptor and effector is the common element that unites a whole battery of senses. The evolutionary roots of our ability to see light and taste sugar are all tied together.

There's another class of senses that seem to function in a different way, and are distinct from the G-protein mediated senses like sight and smell. The G-protein senses are characterized by specific receptors tuned to recognize discrete elements—photons, chemicals, transmitters—in the environment. Sensing thirst, touch, vibration, texture, pressure, though, are different. There the stimulus is physical distortion, not a specific chemical agent. These senses don't use G-proteins, and are less well understood…but it's beginning to look like there are commonalities here, too, and we can trace our ability to hear and touch to a bacterium's ability to react to changes in salt concentrations.

What Kung proposes is that there are two very broad classes of primitive sensory signalling: one that detects solutes, molecules dissolved in the environment, which has diversified over evolutionary history to handle vision, smell, and taste; and another class that detects solvents, which has evolved to be used in our senses of hearing and equilibrium and touch. One way to think of it is that a bacterium's ability to sense when it is raining is the precursor to our ability to listen to music.

Here, for example, is a rod-shaped E. coli bacterium in an environment with some concentration of salts dissolved in it; it's in equilibrium. If it rains, though, turning our salty red world into a more dilute pink one, water flows into the bacterium, causing it to swell distressingly. The dangerous turgor pressure is detected by sensors that respond to the distortion of the membrane, opening pores large enough for internal solutes to flow out, restoring equilibrium and allowing the bacterium to relax back into its rod shape.

An E. coli cell in a normal environment (left) and in the rain (or upon dilution in the laboratory, right). A bacterium (shown as a rod), having adjusted its cytoplasm to the relatively high osmolarity of the surrounding milieu (shown in dark red, the red dots being solutes, not water), is confronted with a sudden dilution of its environment upon the onset of rain (light red). Entry of water (not shown) through the lipid bilayer swells the bacterium (now oval-shaped) and stretches open the MS channels to jettison solutes (red puffs), enabling it to reach a new equilibrium and escaping osmolysis (and returns to being rod-shaped).

So how do proteins detect the swelling of the cell? The answer is surprisingly direct: they have channels that respond to the tension in the cell membrane. Here, for example, is the MS (mechanosensitive) channel in E. coli. It contains a ring of helically organized rods that allow the channel to dilate open like the iris of a camera as the lipids in the membrane around it push and pull on its structure.

Helical segments (S1, S2, S3) and transmembrane helices (M1, M2) in one MscL subunit, as deduced from sequence and other analyses (left). Side (upper centre) and top (lower centre) views of the closed channel backbone structure of the E. coli MscL protein, by analogy to the crystal structure of the M. tuberculosis MscL homologue. The open structure deduced from both modelling and experimentation (right). Unlike MthK, the prokaryotic K+ channel that is equipped with a second constriction (the K+ filter), MscL is like the acetylcholine receptor/channel, in which the open gate doubles as the filter. Here the opening is huge (30 Å in diameter): befitting its ability to release solutes indiscriminately. The work to increase the area under tension constitutes the free energy difference that partitions the open and closed states.

These pores don't require any accessory proteins to do their job: they can be inserted into artificial lipid membranes, and they still function, responding to to distortion of the membrane by changing their permeability, which can be measured as a flow of current. Another interesting property is that they are sensitive to the lipid content of their surrounding membrane, which changes the forces exerted on them. Many anesthetics are readily dissolved in membrane lipids, and this may explain their mode of action—the E. coli MS channels can respond to exposure to procaine and tetracaine. That shot of painkiller you get at the dentist may work by making your nerve cell membranes more fluid and slippery, changing the way they can exert force on pain receptor channels.

We animals have other kinds of mechanoreceptors. Hair cells, indispensable for hearing and balance, rely on elaborate cilia coupled to TRP (transient receptor potential) channels in the membrane with tethers—tug on a hair, and it pulls or pushes on a structure imbedded in the membrane. The principle is the same, though, with tension between a protein and the lipids around it inducing a change in channel properties.

TRP channels have been located in complex auditory sensory cells, even though the mechanism by which ciliary vibrations (arrow pairs) lead to the iris-like opening of the channels on the side of the cilia is not clear. a, The antennal chordotonal organ of Drosophila. CM, cap-cell matrix; DC, dendritic cap; CD, ciliary dilation. Red marks the location of NAN (a TRPV-type channel subunit encoded by the Nanchung gene). b, A vertebrate hair cell. St, stereocilia; K, kinocilium; PZ, pericuticular zone. Red marks the location of TRPA1. c, Models of the vertebrate hair-cell transduction channel. Molecular identifications have transformed the biophysical trapdoor model (left) to one with a TRPA channel and a stiff cadherin-containing tip link (right). The elastic element of transduction is now assigned to the ankyrin repeats in the four (presumably) TRPA subunits (shown as coils), which are presumed to be attached to cytoskeleton and/or myosin (not shown). This current model is compatible with one in which the displacement of the channel protein, with respect to the lipid bilayer, ultimately triggers the channel conformation change, right. However, none of these models should be taken literally since we do not yet know the true composition of the transduction channel(s) and how the various channel components contact each other and the lipids.

I'm feeling the keys under my fingers and seeing the screen in front of me and hearing the music on my headphones using a suite of tools derived from some primeval microbe's acquisition of sensors for dissolved nutrients and osmotic pressure. We've elaborated and refined and added new layers of complexity, but deep down we can still see echoes of our microscopic ancestors.

a, A diagram of an imaginary early cell equipped with two types of receptors that are required to sense solutes and solvents—the two ingredients of life's chemistry. The dots in the grey background represent water molecules (the solvent) and the red circles represent solutes (molecules dissolved in water). When a cell accumulates solutes, the internal water concentration is reduced and the tendency of water to enter the cell results in a turgor. Both the lock-and-key type of receptors (red) for different solutes (ligands), as well as the turgor sensors (blue) for water (the solvent), are needed for even an early cell to survive. b, A hypothetical diagram (not to be mistaken for phylogenetic trees) on the grouping of various senses that emphasizes the discrete separations of the lock-and-key type of sensing of the solutes (red) from the force-from-bilayer type of sensing of the solvent (blue).

Some people seem to think the linkage to our history demeaning, and take offense at being found similar to an ape. Personally, I find it uplifting and wonderful to see our unity with bacteria, fungi, worms, jellyfish, herps, and fish. What I love about biology is the way it binds us closer and closer to the world around us, and shows us over and over again that we're part of this place.

Kung C (2005) A possible unifying principle for mechanosensation. Nature 436:647-654.