Cellular Machines Work Like Cameras, Winches and Turboprops
The discovery that cells are filled with molecular motors is one of the major achievements of late 20th-century molecular biology. Biochemists routinely use the word “motor” when describing cellular processes, because, in fact, machines made of protein actually do use energy to perform work. Now we have a new hybrid science – biophysics – that analyzes the kinetics of tiny machines that work just like human-sized ones, but at scales a billion times smaller.
The diversity of forms these motors take, and the efficiency of their operations, is really quite astonishing. Here are just a few recent examples from the literature.
- Camera Iris: One of the many gate motors in the cell membrane acts like a camera iris. Biochemists in Scotland studied a mechanically sensitive channel named MscS in the E. coli bacterium. At 3.45 angstrom resolution (a third of a billionth of a meter), they found that the protein coils in this channel, which opens in response to mechanical energy, twist in a way that opens and closes like the iris of your eye. The motion breaks a vapor lock, they said; “This motion is akin to the opening of camera iris.” The side chains move apart “in a manner reminiscent of the plates of a mechanical camera iris.” In conclusion of their paper in Science,1 they said:
The opening and closing of channels is central to biology, yet is still poorly understood at a molecular level. The use of mutants with modified gating kinetics may prove a widely applicable approach to crystallize different channel conformations. By combining functional data with an open structure of the MscS channel, we have described the transitions between closed and open forms that involve tilting and separation of the transmembrane helices reminiscent of a camera iris.
- Winch: Like men pulling together, cell motors can team up to pull cargo along. The two primary transport motor types, dynein and kinesin, actually “walk” step-by-step on filaments. Like African women with baskets on their heads, these machines attach to vesicles and other cargo and carry them to their destinations. Scientists are finding that more often than not they work in teams.
This is an active area of research with many questions. William Hancock (Penn State) reviewed what is known in a Dispatch in Current Biology.2 He asked some of the questions: “how many motors need to be turned on or off to trigger directional switching? And what sorts of regulation and cooperative interactions underlie the complex oscillations of chromosomes seen during metaphase?” As if individual motors were not complex enough, he said, “While understanding the characteristics of the individual motors involved in these processes is important, there is clearly another level of complexity that needs to be considered when developing realistic physical models of these processes.”
- Flagellum motorboat: Observers of the evolution controversy will immediately recognize the bacterial flagellum as the mascot of the intelligent design movement (02/10/2003, 07/11/2003, 10/27/2004). Evolutionists are just as astonished with this outboard motor, present in one of the “simplest” forms of life, but continue to believe it evolved somehow. An example is Dr. Flagellum himself, Howard Berg of Harvard (07/11/2003, 08/19/2005, 06/24/2008). This man who knows the most about the physics of the flagellum published a handy-dandy Q&A article about the flagellum in the Aug. 26 issue of Current Biology.3
Some quick facts from his Quick Guide: It is “remarkably small rotary electric motor” with a drive shaft, rotor, stator, bushings, universal joint, mounting plate and switch complex. It runs on proton motive force or sodium ions that come through the cell membrane through specialized channels. It responds to chemical gradients with higher rotation. “At high loads, eight or more force-generating elements are active, each generating the same torque.” Some 20 protein parts make up the motor base, but many additional parts are involved during its construction. The motor is built from the inside out with parts added in a strict sequence:
There are a number of checks and balances in this process, the most dramatic of which involves an antibody-like factor that blocks expression of late genes, which encode the filament protein FliC, the Mot proteins A and B, and the various components of the chemotaxis pathway. When motor assembly reaches the level of the hook, this factor is pumped out of the cell by the flagellar transport apparatus, relieving suppression of late-gene transcription. At about the same time, the export apparatus switches from transport of components of the rod and hook to the hook-associated proteins and filament. Ingenious mechanisms are involved in supplying raw material at the base of the motor, in rod and hook-length control, and in pumping hook and filament subunits through a 2 nm pore along the motor axis. In Escherichia coli and Salmonella, the energy required for this export is supplied by an electrochemical proton gradient (protonmotive force). Remarkably, the filament grows at its distal end.
(Links to animations of this process can be found in the 11/02/2005 entry). Berg continues: the motor can turn both directions, and stop in a millionth of a rotation. It usually reverses direction once per second. This allows the organism to alter direction quickly. The viscosity the bacterium feels in water is similar to what you would feel swimming in molasses. The propeller has variable pitch. Rotation is likely driven by conformational changes of protein parts between the 26 units comprising the ring. The flagellum usually spins at 100Hz (6,000 RPM), but can go 300Hz (18,000). Flagella with sodium-ion drive can go five times faster (~100,000 RPM).
Berg did a little calculation of how much force the motor generates. If ramped up to our scale, he said, it would be about 5 horsepower per pound – “That’s roughly the power per pound generated by a turboprop airplane engine.” Unlike the airplane engine, though, the flagellum doesn’t get hot: “the motor is water-cooled and thermal diffusion is very efficient over small distances, so its temperature remains very close to ambient.”
Asked if the flagellar motor is good for anything, Berg remarked, “If you are a bacterium, a great deal: a lot of energy is expended in building such a machine so that a cell can find essential nutrients. For humans, very little so far, except to illustrate how extraordinary nanotechnology can be.”
Of the articles cited above, only Berg’s discussed evolution. He compared the flagellum to the simpler, needle-shaped Type III Secretory System (TTSS; see 04/17/2007, bullet 11, and 01/05/2007). “Some argue that the flagellar rotary motor evolved from the needle structure, but it was probably the other way around, since flagellated bacteria existed long before their eukaryotic targets,” he said. This puts the more-complex machine first – opposite what evolutionary theory would predict. “Perhaps they evolved from a common ancestor,” he continued. But then he asked, “What was the rotary motor doing before the helical propeller was invented, if indeed that was the order of events? Serving as a secretory apparatus that acquired the ability to spin? Packaging polynucleic acids into virus heads? Food for thought.”
1. Wang, Black, Edwards, Miller, Morrison, Bartlett, Dong, Naismith and Booth, “The Structure of an Open Form of an E. coli Mechanosensitive Channel at 3.45 Angstrom Resolution,” Science, 29 August 2008: Vol. 321. no. 5893, pp. 1179-1183, DOI: 10.1126/science.1159262.
2. William O. Hancock, “Intracellular Transport: Kinesins Working Together,” Current Biology, Volume 18, Issue 16, 26 August 2008, Pages R715-R717, doi:10.1016/j.cub.2008.07.068.
3. Howard Berg, “Quick guide: Bacterial flagellar motor,” Current Biology, Volume 18, Issue 16, 26 August 2008, Pages R689-R691, doi:10.1016/j.cub.2008.07.015.
Food for thought, indeed. OK, so chew on it. Howard Berg wants us to think that the complete rotary engine existed for some other function before it was co-opted by the bacterium as an outboard motor. That’s like believing a water-cooled, precision-assembled, variable-pitch, reversible, switch-controlled, highly efficient 5HP/lb airplane turboprop engine composed of 40 essential parts just “emerged” from nowhere until an airplane chassis “emerged” that used it to fly. We thought about it. We chewed on it. We ruminated on it. We masticated it. We munched, crunched, chomped, chawed and gnawed it to pulp. Bleagh. So we spit it out and had some SOLID* food for thought instead.
*Smart Ones Like Intelligent Design.