Mechanics of Motor Proteins and the Cytoskeleton , Jonathon Howard Sinauer Associates, Sunderland, Mass., 2001. $59.95 (367 pp.). ISBN 0-87893-334-4
Modeling and computational methods in cell and molecular biology are becoming as important as more traditional experimental techniques of biophysics and biochemistry. Indeed, theory has contributed a great deal to our understanding of molecular motors, the protein machines that convert chemical energy directly into mechanical work. Just nanometers in size, they can move thousands of nanometers per second and generate forces in the piconewton range. Many of these motors use the actin and microtubule filaments of the cytoskeleton as dynamic “tracks,” which the cell assembles where and when they are needed. In fact, the cytoskeletal polymers themselves can generate sufficient force as they polymerize or depolymerize to drive organelle movements. Some motors work alone or in small numbers (kinesin, myosin V), while others work in concert with many partners (myosin II). Despite this diversity, unifying principles have emerged according to which protein motors operate.
Traditionally, biologists characterize energy conversion using a free-energy diagram. But thermodynamics gives only a very limited picture and cannot address the issue of mechanism. Over the last 10 years, single-molecule techniques and structural-studies experiments, complemented by quantitative modeling, have provided a more mechanistic view of the functioning of motor proteins and cytoskeletal polymers and of the cell motility. Quantitative analysis of load–velocity curves and motion statistics for single molecules provide answers to the longstanding questions: How do these proteins move? How much “fuel” do they consume? How is this fuel converted into mechanical force?
Answering these questions requires knowledge of classical mechanics at a level covered in many physics textbooks. However, these books deal mainly with macroscopic systems, while mechanics on the molecular level is dominated by Brownian motion. Thermal fluctuations smear out deterministic trajectories and serve as a lubricant that allows molecules to surmount high energy barriers. All this leads to surprising and counterintuitive behaviors. What has been missing from the literature is an introductory treatment of this realm of classical physics that can be grasped by a biological audience.
Jonathon Howard’s Mechanics of Motor Proteins and the Cytoskeleton fills this void, providing a physical foundation for cell mechanochemistry for students of biology, physics, mathematics, and engineering. Other books cover similar biological ground, but do not cover the physics of cell motility.
Howard is well suited to writing a textbook about cytoskeletal mechanics; he has done important work on the mechanochemistry of cytoskeletal molecules and is one of the foremost researchers on kinesin.
The first part of the book introduces the basic concepts of classical mechanics and statistical physics necessary to treat a protein as a machine built from elastic rods, joints, levers, and latches. While these beginning chapters are likely to be quite familiar to physicists and engineers, they will surely be very useful for biology students. Even readers familiar with the physics will benefit from the plentiful examples, analysis of length and time scales, and back-of-the-envelope estimates for building intuition about a microscopic scale. Moreover, Howard treats carefully and clearly the difficult topic of the coupling between mechanical forces and chemical reactions.
The second and third parts of the book are devoted to the mechanics of the cytoskeletal filaments and motor proteins, respectively. This material will be challenging for students of all disciplines. Physicists and engineers will learn the importance of the voluminous structural and biochemical data about actin, microtubules, myosin, and kinesin. Biologists will be introduced to methods for applying the quantitative apparatus of the first part to modeling the cytoskeleton. Chapter two explains the phenomena of force generation by filament polymerization, treadmilling, and dynamic instability of biopolymers. The last part of the book introduces the concepts of motor-duty ratio, the mechanochemical cycle, force–velocity relations, and the role of thermal fluctuations in force generation. Comparisons between structures and mechanochemical cycles of kinesin and myosin give a glimpse of the diversity of molecular motors and illustrate some unifying principles of molecular mechanics.
The book is not without shortcomings. Howard discusses only the mechanical properties of individual filaments, ignoring the rheology of cross-linked actin gels and actin dynamics at the leading edge of migrating cells. Some well-studied (and extensively modeled) motors, such as ATP synthase and RNA polymerase, deserve detailed description in this book, but are all but ignored. The elementary hand-overhand model for kinesin at the end of the book is too primitive and somewhat misleading. However, these minor faults can be overcome in subsequent editions. Moreover, the persistent and curious student can—and must—complement the book by reading recent reviews by Paul Janmey (Results Probl. Cell Differ. 32, 181 [2001]), Gary Borisy (Curr. Opin. Cell Biol. 12(1), 104 [2000]), Ron Vale (Trends Cell Biol. 9(12), M38 [1999]), George Oster (Biochem Biophys Acta 1458(2–3), 482 [2000]), and others. Altogether, this is an excellent multidisciplinary book that will help educate a new generation of researchers in the field of quantitative biology.
