Molecular and Cellular Biophysics

Jack A. Tuszynski

• Publisher: Chapman and Hall/CRC
• Year: 2018
• ISBN:
  9781315357256
• Edition: 1
• Topic: Naturwissenschaften
• Subtopic: Physik

From quantum theory to statistical mechanics, the methodologies of physics are often used to explain some of life's most complex biological problems. Exploring this challenging yet fascinating area of study, Molecular and Cellular Biophysics covers both molecular and cellular structures as well as the biophysical processes that occur in these structures. Designed for advanced undergraduate and beginning graduate students in biophysics courses, this textbook features a quantitative approach that avoids being too abstract in its presentation.Logically organized from small-scale (molecular) to large-scale (cellular) systems, the text first defines life, discussing the scientific controversies between mechanists and vitalists, the characteristics of living things, and the evolution of life. It then delves into molecular structures, including nucleic acids, DNA, RNA, interatomic interactions, and hydrogen bonds. After looking at these smaller systems, the author probes the larger cellular structures. He examines the cytoplasm, the cytoskeleton, chromosomes, mitochondria, motor proteins, and more. The book concludes with discussions on biophysical processes, including oxidative phosphorylation, diffusion, bioenergetics, conformational transitions in proteins, vesicle transport, subcellular structure formation, and cell division.

Chapter 1

What Is Life?

1.1 Hierarchical Organization of Knowledge

Every branch of science is more than a collection of facts and relations. It is also a philosophy within which empirical facts and observations are organized into a unified conceptual framework providing a more or less coherent concept of reality. Since biology is the study of life and living systems, it is simultaneously the study of human beings and as such can become biased by our philosophical and religious beliefs.

Understandably, bio-philosophy has been the battleground for the two most antagonistic and long-lived scientific controversies between mechanism and vitalism. Mechanism holds that life is basically no different from non-life, both being subject to the same physical and chemical laws, with the living material being simply more complex than the non-living matter. The mechanists firmly believe that ultimately life will be totally explicable in physical and chemical terms. The vitalists, on the other hand, fervently argue that life is much more than a complex ensemble of physically reducible parts and that there are some life processes that are not subject to the normal physical and chemical laws. Consequently, life will never be completely explained on a physiochemical basis alone. Central to the vitalists’ doctrine is the concept of a “life force”, ‘vis vitalis’ or ‘elan vital’, a non-material entity, which is not subject to the usual laws of physics and chemistry. This life force is seen to be animating the complex assembly of biomolecules into an organism and making it “alive”. This concept is both ancient and virtually universal, having appeared in some form in all cultures and providing the basis for the religious beliefs of most of them.

It is to the early Greek philosopher-physicians such as Hippocrates that we owe the first organized concepts of the nature of life. These concepts developed within the framework of the medicine of that time and were based upon a modest amount of clinical observation and much conjecture. All functions of living things were the result of “humors”, i.e., liquids of mystical properties flowing within the body. Several centuries later, Galen, virtually single-handedly, founded the sciences of anatomy and physiology. He produced a complete, complex system based upon his anatomical observations and an expanded concept of Hippocrates’ humors. Galen’s ideas became readily accepted and rapidly assumed the status of dogma, remaining unchallenged for more than a thousand years.

In the mid-sixteenth century, Andreas Vesalius questioned the validity of Galen’s anatomical concepts and performed his own dissections upon the human body publishing his findings in a book, entitled in Latin De humanis corporus fabricus in 1543, which was the first anatomical text based upon actual human dissection. In 1628 William Harvey published the first real series of physiological experiments, describing the circulation of blood as a closed circuit, with the heart as the pumping agent. Vitalism, however, was still the only acceptable concept and Harvey naturally located the “vital spirit” in the blood.

At mid-century, René Descartes, the great French mathematician, attempted to unify biological concepts of structure, function and mind within a frame-work of mathematical physics. In Descartes’ view all life was mechanical with all functions being directed by the brain and the nerves. To him we owe the beginning of the mechanistic concept of living machines-complex, but fully understandable in terms of physics and chemistry. Even Descartes did not break completely with tradition in that he believed that an “animating force” was still necessary to give the machine life “like a wind or a subtle flame” which he located within the nervous system. At about the same time Malphighi, an Italian physician and naturalist, using the new compound microscope to study living organisms, revealed a wealth of detail and complexity in living things.

Continued progress in the biological sciences has pushed the vitalistic viewpoint further and further to the fringes of reputable science. The universe is estimated to be 14–16 billion years old, the solar system is roughly 4.6 billion years old while life on Earth is believed to have emerged 3.5–4 billion years ago. Life is a process commonly described in terms of its properties and functions including self-organization, metabolism (energy utilization), adaptive behaviors, reproduction and evolution. As mentioned earlier, the two main approaches historically developed to understand the nature of the living state are: (i) mechanism or functionalism and (ii) vitalism. Functionalism implies that life is independent of its material substrate.

For example, certain types of self-organizing computer programs (lattice animals, Conway’s game of life, etc.) exhibit life-like functions, a so-called “artificial life”. Furthermore, all the components of living matter are in turn composed of “ordinary” atoms and molecules. This apparently demystifies life that is viewed as an emergent property of biochemical processes and functional activities. The failure of functionalism can be seen in its inability to consider the “unitary oneness” of all living systems. In 19th century biology (Lamarck) the latter characteristic of living systems was called the life force, elan vital, life energy and was assumed to be of electromagnetic nature. Molecular biology has systematically pushed vitalists (“animists”) out of the spotlight viewing electromagnetic effects associated with life as just that: effects but not causes.

An interesting aspect of the organization of science has been very lucidly explained by A.C. Scott [31] in his book “Stairway to the Mind”. In a nutshell, each branch of science exists almost autonomously on the broad scientific landscape developing its own set of elements and rules governing their interactions. For example, for all intents and purposes condensed matter physics, other than using electrons and protons as its main building blocks for solid state systems, exists completely apart from elementary particle physics. By extension, biology, as long as it refrains from violating the principles of physics, should have very little in common with physics. This hierarchical organization of knowledge where there is only a tiny set of intersections between the hierarchies involves

• human society

• culture

• consciousness

• physiology of an organism

• autonomous organs

• assembly of neuronal assemblies (brain)

• assembly of neurons (or other types of cells)

• the multiplex neuron (or any other type of cell)

• the axon-dendrite-synapse system

• mitochondria-nucleus-cytoskeleton

• protein-membrane-nucleic acid systems

• phospholipid-ATP-amino acid systems

• inorganic chemistry

• atomic physics-molecular physics

• nuclear physics

• elementary particle physics

This concept is illustrated schematically in Fig. 1.1.

The concept of a combinational barrier explains the rationale for the above, historically developed compartmentalization of the sciences. Mathematician Elsasser [16] coined the term an Immense Number defined as: I = 10¹¹⁰ The reason for the choice of the power in the exponential is that: I = atomic weight of the Universe measured in proton’s mass (daltons) times the age of the Universe in picoseconds (10^–12 s)

FIGURE 1.1: Hierarchical organization of science.

Since no conceivable computer (even as big and as old as the whole universe) could store a list of ‘I’ objects, and even if it could, there would be no time to inspect it, an immense set of objects defines a category that is a virtually inexhaustible arena for intellectual pursuits with no danger of running out of interesting relationships between its elements. Examples of immense sets are: chess games, possible chemical molecules (chemistry), possible proteins (biochemistry), possible nerve cells (neurophysiology), possible ideas (culture), possible tunes (music) and possible types of personalities (psychology). Consequently, both biology and physics are legitimate areas of scientific exploration in their own right that could happily coexist with minimal overlap. What makes this somewhat simplistic separation less applicable to the biology-physics divide is the existence of so-called emergent phenomena. Due to an organizing principle in this hierarchical picture, we can better understand areas on a higher plane by knowing the organization rules for the elements whose roots are in the lower level of the hierarchy. Knowing the interaction principles between electrons and protons certainly helps develop solid state physics. The knowledge of protein-protein interactions should give us a glimpse into the functioning of a dynamical cell. In general, the whole is more than the sum of its parts, so each level of the hierarchy adds new rules of behavior to the structure that emerges.

1.2 General Characteristics of Living Systems

General Characteristics of a Cell

Life is the ultimate example of a complex dynamical system. A living organism develops through a sequence of interlocking transformations involving an immense number of components which are themselves made up of molecular subsystems. Yet when they are combined into a larger functioning unit (e.g., a cell), then so-called emergent properties arise.

For the past several decades, biologists have greatly advanced the understanding of how living systems work by focusing on the structure and function of constituent molecules such as DNA. Understanding what the parts of a complex machine are made of, however, does not explain how the whole system works. Scientific analysis of living systems has posed an enormous challenge and today we are prepared better than ever to tackle this enormous task. Conceptual advances in physics, vast improvements in the experimental techniques of molecular and cell biology (electron microscopy, NMR, AFM, etc.), and exponential progress in computational techniques have brought us to a unique point in the history of science when the expertise of researchers representing many areas of science can be brought to bear on the main unsolved puzzle of life, namely how cells live, divide and how they eventually die.

Cells are the key building blocks of living systems. Some of them are self-sufficient while others co-operate in multi-cellular organisms. The human body is composed of approximately 10¹³ cells of some 200 different types. A typical size of a cell is on the order of 10 microns and its dry weight amounts to about 7 × 10⁻¹⁶ kg. In its natural state, 70% of the contents are water molecules. The fluid contents of a cell are known as the cytoplasm. The cytoplasm is the liquid medium bound within a cell, while the cytoskeleton is the lattice of f...