More Cell Machines Come to Light

The living cell contains thousands of molecular machines converting energy into useful work. Here are just a few that were recently described in journal papers.

Any given week in the Proceedings of the National Academy of Sciences (PNAS), one is likely to find at least a dozen papers about molecular machines in the cell. Papers about biochemistry usually outnumber those in any other field of science. As imaging techniques continue to improve, the study of cellular machines has thrived, giving scientists better looks at the workings of the cell at higher magnification and finer resolution. This trend shows no sign of stopping.

Those who have seen the film Unlocking the Mystery of Life remember the bacterial flagellum—an outboard motor. They may also remember Jed Macosko saying that a cell has “thousands of machines.” Some of the better-known ones, like the rotary engine ATP synthase and the tightrope-walking dynein, may also be familiar. Let’s take a look at samples from this last week’s catalog of machines discussed in one journal, PNAS, to get a taste of the variety of equipment keeping every cell in operation.

The peroxide sensor (PNAS): Hydrogen peroxide, a powerful oxidant, can damage cells. Some types of bacteria have a special machine, OxyR, with four large domains, that sense H2O2 molecules. When a peroxide molecule is captured, one domain of the machine undergoes a “large conformational change” that triggers the regulatory domains into action.

Peroxisome splitter (PNAS): Peroxides, along other reactive oxygen species and long-chain fatty acids are disposed of in a molecular furnace called the peroxisome. This organelle, containing enzymes involved in many metabolic processes, is duplicated by fission, similar to cell division. A molecular scissors named Peroxin 11 is responsible for initiation of the process; the researchers discovered that it is also important for the final step, scission, producing the two daughter organelles. Interestingly, this machine is “conserved” [unevolved] from yeast to mammalians.”

The shape shifter (PNAS): These authors introduce their machine by saying, “Cells constantly sense and respond to mechanical signals by reorganizing their actin cytoskeleton.” They describe how a force applied to the cell membrane triggers a burst of calcium ions that, in turn, triggers actin molecules around the nucleus to reorganize the skeleton. The actin filaments form a “perinuclear rim” that “may function as a kinetic barrier to protect genome integrity until cellular homeostasis is reestablished.”

The volume control (PNAS): This machine is right in the back of your eyeballs. Retina pigment cells must control their volume; how do they do it? There’s a volume-activated anion channel (VRAC) able to respond to swelling by opening its gates to let out excess ions. When this machine breaks because of mutations, macular dystrophy can result.

Powerstroke of the walker (PNAS): This paper says, “Kinesin molecular motors couple ATP turnover to force production to generate microtubule-based movement and microtubule dynamics.” The authors discuss kinesin-14 from fruit flies, and show how its conversion of ATP to motion during the powerstroke is more complicated than thought. Then they say, “These findings are significant because they reveal that the key principles for force generation by kinesin-14s are conserved [i.e., unevolved] from yeast to higher eukaryotes.”

The thermostat (PNAS): A machine call DesK responds to temperature changes (“essential to cell survival”) by triggering a reversible “zipper” mechanism. In bacterial cells, the transmembrane machine switches its shape if the temperature rises on the outside, triggering additional motions on the inside that can switch on other machines that induce other molecular responses. “The reversible formation of a serine zipper represents a novel mechanism by which membrane-embedded sensors may detect and transmit signals.”

The tightrope walker (PNAS): The two-legged robot dynein walks on tightropes of microtubules, carrying cargo around the cell. Its feet (actually called “heads” by biochemists) have to be able to attach to the microtubules, but can switch from one rope to another as they move. This team investigated what happens when tension is applied to the machine. They dynein will slide if applied in one direction, but fasten more firmly in the other direction. This response is regulated by four additional machines (AAA1-4) that each use ATP as well.

The emergency squad (PNAS): One of the worst emergencies in a cell is when both strands of a DNA double helix snap; it can trigger death of the cell or serious malfunction, leading to disease or cancer. Cosmic rays, chemicals or failures in normal cell processes like transcription can cause double-stranded breaks. Fortunately, there’s an emergency response team named NHEJ (non-homologous end-joining) that knows what to do. The researchers used super-resolution microscopy to watch the team build long filaments at either side of the break as one step in the repair process.

A machine is a device that converts energy into work—not just any work, but directed, useful, functional work. The authors of these and many other papers have no hesitation calling these proteins “machines” and “motors.” Scientists have known about enzymes and proteins for well over a century, but understanding that cells operate with actual machines only dates back about 20 years or so. This revelation—that life operates by thousands of tiny mechanical devices—surely deserves to be called one of the most astounding discoveries in the history of science.

One might compare this discovery to zooming in on what happens when a building is built. Perhaps you’ve watched one of those time-lapse films of a construction project. From a distance, you see just the major features taking shape. If you had never seen such a process before, you might assume this is “just what happens” from time to time. Then, as you are given a series of telescopes with higher and higher resolution, with the ability to stop individual frames of the sequence, the true picture becomes increasingly clear. You find hundreds of people down there operating cranes, bulldozers, ropes, pulleys, ramps and trucks. As you zoom in closer, you see them working in squads, communicating with phones, shaking hands, pointing and responding to each other’s actions. Undoubtedly, your appreciation of what’s involved in construction of a building would grow dramatically.

Now shrink that down a billion-fold. Since the first humans opened their eyes and beheld the living world, there was plenty to show design. But we were like the viewer of the construction project from miles away, unaware of the actual way things work. People understood their bodies and the actions of animals or growth of plants at a macro level only: the running of a deer through a forest, the joy of eating good food and the necessity of disposing of waste, the act of sex and the birth of a child. When layers inside the body became exposed on the hunt, or through injury, a little more of the complexity would be apparent. But without detailed knowledge of what makes a heart beat, or what a liver or kidney actually does, these still might be taken for granted. Except for occasional insights from classical scholars like Aristotle, Hippocrates and Galen, the history of modern medicine and physiology only goes back a few centuries out of the thousands of years man has existed. Modern science starting the zoom-in view on the construction view. Leeuwenhoek opened the world’s eyes to the microbial world; he was astonished to see some of them dancing about with elegant motions.

Fast-forward to about 1995 to the present. We are privileged to live in an age of unprecedented discovery, where our view has zoomed in to the range of billionths of a meter. What did we find? Just fluids jostling about, undergoing chemical reactions? No! A thousand times no! We found machines at work in factories, interacting with incredible efficiency. We found libraries of digital code. We found machines reading the code, translating it, and converting it into other machines. We found thermostats, walking robots, rotary engines, emergency response squads, and long-distance communication networks. We found temperature sensors, volume sensors, disposal services, packaging services, and defense systems. Sex was no longer the transfer of a featureless fluid from the male to the female, but a process of unbelievable complexity involving swimming robots carrying gigabytes of information to be joined to a very complex egg cell with more gigabytes of information, triggering a cascade of machines building machines all the way to a complete baby. The growth of a seedling into a plant is no longer to be shrugged off as something that happens from time to time in nature, but a complex interplay of hormones triggering changes to thousands of molecular machines in plant cells. It’s a planet of machinery! Look around and consider how every living organism, from the worm in the soil, to the bee pollinating a flower, to the hummingbird in the garden, to the tree growing higher and higher in your back yard, operates through the action of thousands of molecular machines that we have begun to understand only in the last tenth of 1% of recorded human history.

If the wonder of what we have discovered doesn’t make you shout “Praise the Lord!” as never before, you might be asleep or dead.

Tragically, praise has been the last thing on the minds of many scientists studying these things. A century and a half of Darwinian dogma has blinded their minds to the obvious inference to intelligent design from molecular machines. We find, however, some curious things in these papers. One is the frequent use of “remarkable” by the authors when they uncover something wonderful. Another is the increasing silence about Darwinism as more details come to light. (There’s an inverse relationship between the frequency of evolution-words to the amount of detail in scientific papers about molecular machines.) A third curious thing is biomimetics: i.e., how cellular machines inspire thoughts of copying those designs for human applications. Together, these curiosities in PNAS and other journals hint that the consciences of evolutionary biologists are not completely dead. A flicker of the design inference still burns and may catch fire some day. When it does, it could burn away the Darwinian chaff, liberate philosophy to once again celebrate natural design as real and pervasive, and provide rational grounds for people of understanding in academia to shout unrestrained, “Great is the Lord, and greatly to be praised!“

Any of us can be ahead of our time and do that right now.