Life's Ratchet: How Molecular Machines Extract Order from Chaos

by Hoffmann, Peter M.

  evolution Process by which new proteins, molecular machines, or organisms arise. Novelty is produced by mutations, which are then acted upon by selection. Acts like a “ratchet,” leading to increasing complexity.

  feedback loop The interaction of products of a process with the precursors of a process via allostery, whereby the amount of product is controlled. Feedback loops are the basic component of the chemical “circuitry” that regulates cells.

  Feynman’s ratchet An automated version of Maxwell’s demon, which could extract energy from a system at equilibrium, thus violating the second law of thermodynamics. Shown to be impossible.

  first law of thermodynamics Law of energy conservation, which explicitly includes heat as a type of energy.

  fluorescence Emission of longer-wavelength light by a molecule in response to excitation by shorter-wavelength light.

  fluorophore Molecule that emits visible light when excited by light of shorter wavelength (fluorescence). Used to label molecules so that their behavior can be observed in an optical microscope.

  food calorie Energy unit, equals 4,184 joules.

  force A push or pull that either deforms an object or changes its state of motion. The unit of force is the newton (N).

  free energy Energy that is available to do work. Equals total energy minus unusable, dispersed energy. The latter is given by the product of entropy and temperature.

  Gedankenexperiment Posing a hypothetical situation to see if a physical theory makes sense. From a German word meaning “thought experiment.”

  gene A unit of hereditary information. A complete sequence of information in the genome, encoded in DNA.

  genetic code The code that DNA uses to encode amino acid sequences of proteins.

  head Term for the motor domain of a motor protein, specifically, the part on which it walks.

  helicase Molecular machine that untwists and separates DNA strands during replication.

  holism The view that systems have to be studied as a whole, without being broken into parts.

  hydrophilic Molecules that lower their free energy when dissolved in water. Can either form hydrogen bonds with water, or are charged.

  hydrophobic Molecules that experience an increase in free energy when placed in water, and do therefore not dissolve in water.

  irritability The property of living tissue to react to external stimuli such as electrical currents.

  kinesin Family of molecular motors that move on microtubules. Responsible for moving cargo or assisting in cell division.

  kinetic theory A precursor to statistical mechanics; the application of statistics to the motion of atoms in gases.

  Landauer’s limit The minimum energy required to erase one bit of information.

  laser tweezers Laser-based force measurement technique using a small bead suspended in focused laser light.

  ligase Enzyme that splices parts of DNA together.

  lipids Amphiphilic molecules, which form micelles or vesicles and are the main constituent of cell membranes. Consist of a hydrophobic fatty acid bound to a hydrophilic head group.

  loose coupling The ability of a molecular motor to move variable distance for each ATP consumed. Such a motor must periodically detach from the track and move as a Brownian ratchet.

  Loschmidt’s demon A hypothetical creature that could reverse time.

  macrostate The externally measurable state of a system, which is necessarily an average over many atoms and molecules. Usually described in terms of macroscopic quantities like temperature or pressure.

  Maxwell’s demon Hypothetical creature that could sort molecules and violate the second law of thermodynamics. Shown to be impossible.

  messenger RNA (mRNA) RNA that carries the information to make a protein from DNA in the cell nucleus to the ribosomes outside the nucleus.

  micelle Spherical assembly of amphiphilic molecules.

  micrometer One-millionth of a meter. Typical size of a bacterium.

  microstate The exact state of a system; includes the location and speeds of all atoms in the system.

  microtubules Stiff, protein-based fibers that make up part of the skeleton of the cell. Kinesin and dynein move on microtubules. Microtubules play an important role during cell division.

  mitochondria Power plants of cells. This is where sugar is broken down and the energy contained is transferred to ATP.

  mitosis Cell division.

  MMP (matrix metalloprotease) An enzyme that breaks down the extracellular matrix and frees up cells so they can move. Some MMPs have been shown to be molecular machines that derive their energy from eating collagen.

  molecular machine Molecule that can transform energy from one form to another.

  molecular motor Molecular machine that transforms chemical into mechanical energy.

  molecular storm Random thermal motion of atoms and molecules.

  molecule Tightly bonded assembly of at least two atoms. In biological cells, some molecules, such as DNA or proteins, can be very large, containing many thousands of atoms.

  mutation Irreversible change in a gene; the result of a chemical reaction of DNA with an ion or a radical (atoms, molecules, or ions with unpaired electrons).

  myosin Family of molecular motors that move on actin. Myosin II is responsible for muscle contraction, while myosin V transports cargo within cells.

  nanobots Hypothetical nanoscale machines that can perform complex tasks, especially with medical applications.

  nanometer One-billionth of a meter. Typical size of a small molecule.

  nanoscale The scale of the nanometer.

  nanoscience The science of nanoscale objects.

  nanotechnology Technology that involves nanoscale structures or materials.

  normal distribution Distribution expected for measurements that depend on several statistically independent influences. This universal distribution is found in physics, biology, economics, and other fields.

  nucleotide Molecule that makes up a “letter” in the genetic code. Part of DNA and RNA. There are four nucleotides in DNA: adenine, guanine, thymine, and cytosine, denoted by the letters A, G, T, and C.

  open system Systems that can exchange energy or matter, or both, with the environment; as opposed to isolated systems.

  perpetuum mobile Machine that could violate the first, or at least the second, law of thermodynamics. Found to be impossible.

  polymerase Molecular machine that makes (polymerizes) DNA or RNA.

  power Rate of transformation of energy into a different form, or rate of work performed. Energy per second. The unit of power is the watt (W); 1 watt = 1 joule per second.

  pressure Force per unit area. In a gas, pressure is the result of many collisions of atoms with a wall.

  probability The likelihood of the occurrence of an event; given by the number of ways the event could occur, divided by all possible outcomes.

  processivity The ability of a molecular motor to move on a molecular track for long distances without detaching.

  protein A large molecule consisting of a folded strand of amino acids connected by peptide bonds. Proteins fold into specific shapes, which allow them to fulfill many tasks in cells, including acting as enzymes, molecular machines, or structural elements (collagen, actin, etc.).

  protein folding Physical process in which a chain of amino acids folds into its lowest free-energy state to form a functional protein.

  quantum mechanics Physical theory that describes atoms, electrons, and subatomic particles. Fundamentally based on probabilities.

  reductionism A method in which systems are analyzed by breaking them into smaller parts.

  replication The copying of DNA during cell division.

  ribosome RNA-based machine in our cells that produces proteins according to instruction contained in DNA.

  RNA (ribonucleic acid) Molecule that can both carry information and act as a catalyst. Plays many roles in cells, from information carrier to protein production machines (ribosome).
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br />   scanning probe microscopy Type of microscopy where a sharp probe “feels” a surface to generate an image or to measure surface properties.

  scanning tunneling microscopy A type of scanning probe microscopy that measures tunneling currents between a sharp metallic needle and a conducting surface. Can provide images of atoms.

  second law of thermodynamics Law that states that in a closed system, entropy can never decrease, but generally tends to increase during energy transformations. There are many alternative formulations of this law.

  statistical mechanics The application of statistical methods to the motions of atoms and molecules. Averaging over many atoms and molecules leads to the macroscopic science of thermodynamics.

  systems biology Mathematical theory of regulation and computation in living cells.

  temperature The average kinetic energy of atoms or molecules in a system at equilibrium.

  thermodynamics The science of heat and energy, volume, pressure, and temperature.

  tight coupling The exact coupling of ATP hydrolysis to the motion of a molecular motor. Typically implies that one ATP is hydrolyzed for each step taken by the motor. Associated with motors that have at least one part of the motor attached to the track at all times. As opposed to loose coupling.

  Topoisomerase Enzyme that cuts and reattaches DNA strands to relieve strain and keep DNA from tangling during replication.

  transcription The transferring of information from DNA to messenger RNA.

  transfer RNA (tRNA) RNA–amino acid complexes that contain the key to translate the genetic information into a protein.

  transition state “Uncomfortable” state that molecules find themselves in temporarily as they transform from one stable form to another. Energy associated with the transition state is the activation barrier.

  translation Translating genetic information into a protein. Happens in the ribosome, with the aid of transfer RNA (tRNA).

  vesicle Spherical assembly of lipids; consists of a double-walled sphere separating a water-filled chamber from water on the outside of the vesicle.

  vitalism The belief that life is associated with special forces.

  work The product of force and distance; the expenditure of energy when force acts over a certain distance to move an object. The unit of work is the joule (J), which is equal to a newton-meter (N·m).

  X-rays Highly energetic electromagnetic radiation, generated by bombarding high-speed electrons into a metal target.

  Sources

  This a partial list of sources I used to write the book. Many of these sources were used in multiple chapters. However, to save space, each source is mentioned only once for the chapter in which it was used first. The references are listed alphabetically by last name of author. I listed only the sources that are easily accessible. Unfortunately, many technical papers are both inaccessible to the public and often incomprehensible to the nonexpert.

  INTRODUCTION

  Monod, Jacques. Chance and Necessity. Translated by Austryn Wainhouse. New York: Alfred A. Knopf, 1971.

  Schrödinger, Erwin. What Is Life? Canto ed. Cambridge: Cambridge University Press, 1992.

  Thomson, D’Arcy. On Growth and Form. Canto ed. Cambridge: Cambridge University Press, 1992.

  CHAPTER 1

  Alioto, Anthony. A History of Western Science. Englewood Cliffs, N.J.: Prentice-Hall, 1986.

  Aristotle. De Anima. In The Basic Works of Aristotle. New York: Modern Library, 2001.

  ———. Physics. In The Basic Works of Aristotle. New York: Modern Library, 2001.

  Cahan, David. Hermann von Helmholtz and the Foundations of Nineteenth-Century Science. California Studies in the History of Science. Berkeley: University of California Press, 1994.

  Darwin, Charles. The Origin of Species. Available at Literature.org, the Online Literature Library, www.literature.org/authors/darwin-charles/the-origin-of-species/.

  Debus, Allen George. Man and Nature in the Renaissance. Cambridge Studies in the History of Science. Cambridge: Cambridge University Press, 1978.

  Descartes, René. Discourse on Method. Available at Literature.org, the Online Literature Library, www.literature.org/authors/descartes-rene/reason-discourse/.

  Gay, Peter. The Enlightenment: The Rise of Modern Paganism. New York: W. W. Norton, 1995.

  Granger, Herbert. Aristotle’s Idea of the Soul. Boston: Kluwer, 1996.

  Hankins, Thomas. Science and the Enlightenment. Cambridge Studies in the History of Science. Cambridge: Cambridge University Press, 1985.

  Harris, Henry. The Birth of the Cell. New Haven, Conn.: Yale University Press, 2000.

  Helmholtz, Hermann. Über die Erhaltung der Kraft. Available at The Internet Archive, www.archive.org/details/berdieerhaltung01helmgoog.

  Henry, John. The Scientific Revolution and the Origins of Modern Science. Studies in European History. New York: Palgrave Macmillan, 2008.

  Holmes, Richard. The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science. New York: Pantheon, 2009.

  Hooke, Robert. Micrographia. Available at Project Gutenberg, www.gutenberg.org/files/15491/15491-h/15491-h.htm.

  La Mettrie, Julien. Machine Man and Other Writings. Edited by Ann Thomson. Cambridge: Cambridge University Press, 1996.

  La Mettrie, Julien, and Aram Vartanian. La Mettrie’s L’homme Machine: A Study in the Origins of an Idea. Princeton, N.J.: Princeton University Press, 1960.

  Lenoir, Timothy. The Strategy of Life: Teleology and Mechanics in Nineteenth-Century German Biology. Chicago: University of Chicago Press, 1989.

  Lindberg, David. The Beginnings of Western Science: The European Scientific Tradition in Philosophical, Religious, and Institutional Context, Prehistory to A.D. 1450. Chicago: University of Chicago Press, 2008.

  Lucretius. De Rerum Natura. Available at The Internet Classic Archive, http://classics.mit.edu/Carus/nature_things.html.

  McKendrick, John Gray. Hermann Ludwig Ferdinand von Helmholtz (Masters of Medicine). New York: Longmans, Green & Co., 1899.

  Mendelsohn, Everett. Heat and Life: The Development of the Theory of Animal Heat. Cambridge, Mass.: Harvard University Press, 1964.

  Newton, Isaac. Opticks. Available at Project Gutenberg, www.gutenberg.org/files/33504/33504-h/33504-h.htm.

  Rubenstein, Richard. Aristotle’s Children: How Christians, Muslims, and Jews Rediscovered Ancient Wisdom and Illuminated the Middle Ages. New York: Houghton Mifflin, Mariner Books, 2004.

  Russell, Bertrand. A History of Western Philosophy. New York: Simon & Schuster, 1972.

  Shelley, Mary Wollstonecraft. Frankenstein—or the Modern Prometheus. Available at Literature.org, the Online Literature Library, www.literature.org/authors/shelley-mary/frankenstein/.

  CHAPTER 2

  Chardin, Teilhard. The Phenomenon of Man. Available at The Internet Archive, www.archive.org/details/phenomenon-of-man-pierre-teilhard-de-chardin.pdf.

  Eigen, Manfred, and Ruthild Winkler. Das Spiel—Naturgesetze steuern den Zufall. Serie Piper, 1996; English edition: Laws of the Game: How the Principles of Nature Govern Chance. Princeton, N.J.: Princeton University Press, 1993.

  Judson, Horace Freeland. The Eighth Day of Creation: Makers of the Revolution in Biology. Plainview, N.Y.: Cold Spring Harbor Laboratory Press, 1995.

  Kline, Morris. Mathematics for the Nonmathematician. New York: Dover, 1985.

  ———. Mathematics in Western Culture. New York: Oxford University Press, 1964.

  Mainzer, Klaus. Der kreative Zufall—Wie das Neue in die Welt kommt. Munich, Germany: C. H. Beck, 2007.

  Mlodinow, Leonard. The Drunkard’s Walk: How Randomness Rules Our Lives, New York: Pantheon, 2008.

  Moore, Walter. Schrödinger: Life and Thought. Cambridge: Cambridge University Press, 1992.

  Timoféeff-Ressovsky, N. W.; K. G. Zimmer; and M. Delbrück. Über die Natur der Genmutation und der Genstruktur (the “green pamphlet”). In Nachrichten von der Gesellschaft der Wissenschaften zu Göttingen. Berlin: Weidma
nnsche Buchhandlung, 1935. Available at www.ini.uzh.ch/~tobi/fun/max/timofeeff ZimmerDelbruck1935.pdf.

  Wykes, Alan. Doctor Cardano, Physician Extraordinary. London: Muller, 1969.

  CHAPTER 3

  Feynman, Richard. The Feynman Lectures of Physics. Boston: Addison Wesley Long-man, 1970.

  Lindley, David. Boltzmann’s Atom: The Great Debate That Launched a Revolution in Physics. New York: Free Press, 2001.