Role of biophysics in interdisciplinary science

Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. Biophysical research shares significant overlap, moleculer biochemistry, physical chemistry, physiology, nanotechnology, bioengineering, computational biology, biomechanics, developmental biology and systems biology. Scientists in this field conduct research concerned with understanding the interactions between the various systems of a cell, including the interactions between DNA, RNA and protein biosynthesis, as well as how these interactions are regulated. A great variety of techniques are used to answer these questions.
Fluorescent imaging techniques, as well as electron microscopy, X-ray crystallography, NMR spectroscopy, atomic force microscopy (AFM) and small-angle scattering (SAS) both with X-rays and neutrons (SAXS/SANS) are often used to visualize structures of biological significance. Protein dynamics can be observed by neutron spin echo spectroscopy. Conformational change in structure can be measured using techniques such as dual polarisation interferometry, circular dichroism, SAXS and SANS. Direct manipulation of molecules using optical tweezers or AFM, can also be used to monitor biological events where forces and distances are at the nanoscale.
Molecular biophysicists often consider complex biological events as systems of interacting entities which can be understood e.g. through statistical mechanics, thermodynamics and chemical kinetics. By drawing knowledge and experimental techniques from a wide variety of disciplines, biophysicists are often able to directly observe, model or even manipulate the structures and interactions of individual molecules or complexes of molecules.
In addition to traditional (i.e. molecular and cellular) biophysical topics like structural biology or enzyme kinetics, modern biophysics encompasses an extraordinarily broad range of research, from bioelectronics to quantum biology involving both experimental and theoretical tools. It is becoming increasingly common for biophysicists to apply the models and experimental techniques derived from physics, as well as mathematics and statistics, to larger systems such as tissues, organs, populations and ecosystems. Biophysical models are used extensively in the study of electrical conduction in single neurons, as well as neural circuit analysis in both tissue and whole brain.
Most biophysical research has been carried out by physicists with an interest in biology; therefore, there must be a way by which scientists educated in physics and physical chemistry can find their way into biology and become familiar with problems that may be open to a physical interpretation. Although classically oriented biology departments often offer positions to biophysicists, they are not substitutes for centres in which biophysical research is of central importance.
The biophysicist possesses the ability to separate biological problems into segments that are amenable to exact physical interpretation and to formulate hypotheses that can be tested by experiment. The primary tool of the biophysicist is an attitude of mind. To this might be added the ability to use complex physical theory to study natural objects – for example, that involved in the X-ray diffraction techniques used to determine the structure of large molecules such as proteins. The biophysicist usually recognizes the utility of new physical tools – e.g., nuclear magnetic resonance and electron spin resonance – in the study of specific problems in biology. But he may also, through previous experience in building specialized equipment to solve physical problems, not have to rely on commercially built instruments.
The development of instruments for biological purposes is an important aspect of a new area -applied biophysics. Biomedical instrumentation is probably most widely used in hospitals. Applied biophysics is important in the field of therapeutic radiology, in which the measurement of dose is critical to treatment, and in diagnostic radiology, particularly with techniques involving isotope localization and whole body scanning to aid in tumour diagnosis. As aids in diagnosis and patient care, computers are of increasing importance. Automation of the chemical analyses routinely carried out in hospitals will soon be a reality. The opportunities for the applications of biophysics seem limitless because the lengthy delay between the development of a research instrument and its application means that many scientific instruments based on physical principles already known will be shown to have important potential for medicine.
Interdisciplinary Work: The biophysical approach is unified by a consideration of biological problems in the light of physical concepts, so that biophysics is, perforce, interdisciplinary. Biophysics may be thought of as the central circle in a two-dimensional array of overlapping circles, which include physics, chemistry, physiology, and general biology. Relations with chemistry are mediated through biochemistry and chemistry; those with physiology, through neurophysiology and sensory physiology. Biology, which may be viewed as a general subject pervading biophysical study, is evolving from a purely descriptive science into a discipline increasingly devoted to understanding the nature of the prime movers of biological events. The evolution of biology in these directions has received great impetus from the biophysical and biochemical discoveries of the 20th century. An understanding of the physical principles governing biological effects is the proper end of biophysics.
Areas of Study: The content and methods of biophysics are illustrated by examining several notable contributions to Science.
Protein Structure: Within two days after the initial publication of Wilhelm Röntgen’s discovery of X rays in 1895, a surgeon in Scotland used X-rays to observe a needle as he extracted it from the palm of an unfortunate seamstress. Although this medical application resulted in the development of radiological diagnosis and treatment of disease by radiation, physical aspects of
Röntgen’s discovery also provided the means for elucidating the structure of proteins and other large molecules. The laws governing the diffraction of-X rays were discovered by the two Braggs, Sir William and Sir Lawrence, who were father and son. At the Cavendish Laboratory at the University of Cambridge, where Sir Lawrence was professor, J.D. Bernal was studying the use of X-ray diffraction for the determination of the structure of large biological molecules. He had already used X-rays to define the size and shape of the tobacco mosaic virus and showed it to have a regular internal structure.
At the Cavendish Laboratory the group that formed around Bernal, a man of wide public and scientific interests, included the Nobel Prize winners Max Perutz and John Kendrew, who in 1937 began to use-X rays to analyze two proteins fundamental to life, myoglobin and hemoglobin, both of which function in the transport of gases in the blood. Twenty-two years passed before the structures of these proteins were established; the significance of the work is that it provided the basis for an understanding of the mechanism of the action of enzymes and other proteins, an active and fruitful subject of modern investigation.
The nerve impulse: Important aspects of biophysics have been derived from physiology, especially in studies involving the conduction of nerve impulses. One important scientific product of World War-II – the development of vastly improved electronics – largely resulted from radar devices that had been used primarily for locating aircraft. Another product, the atomic bomb, was constructed by way of nuclear reactors that could, in peace time, provide an abundant supply of radioactive isotopes, which are now of great value not only in biophysical research but also in biochemistry and medicine. These two disparate advances were important to the work of two Nobel Prize winners, Alan Hodgkin and Andrew Huxley, who showed how the flow of sodium and potassium across the membranes of nerves can be coupled to produce the action potential, a brief electrical event that initiates the action potential, which propagates the nervous signal.
A model of the nerve axon proposed by Hodgkin and Huxley grew from a 19th-century confluence of ideas. Julius Bernstein, an experimental neurophysiologist, used physical chemical theories to develop a membrane theory of nervous conduction; Hodgkin’s initial experiments were designed to test specific predictions of the Bernstein hypothesis. Early in 1938 Hodgkin learned of the important results of a newly developed technique that allowed examination of the time course of nervous conduction. After World War-II, Hodgkin, joined by Huxley, again took up the research. They presented their explanation of the mechanism of nervous conduction in five scientific papers between October 1951 and March 1952.
Biological membranes: The availability of radioactive isotopes provided the technology necessary for understanding how molecules are transported across biological membranes, which are the very thin boundaries of living cells; the environment maintained by membranes in cells differs from the external environment and permits cellular function. The Danish physiologist August Krogh laid the groundwork in this subject; his pupil, Hans Ussing, developed the conceptual means by which the transport of ions (charged atoms) across membranes can be identified. Ussing’s definition of active transport made possible an understanding, at the cellular level, of the way in which ions and water are pumped into and out of living cells in order to regulate the ionic composition and water balance in cells, organs, and organisms. The molecular mechanism by which these processes occur, however, remains to be discovered.
In addition to the function of transport, membranes also are utilized as templates on which such molecules as enzymes, which must function in a sequential fashion, can be kept in the requisite order. Although great progress has been made in understanding the mechanisms by which specific atoms are assembled into large biological molecules, the principles involved in the assembly of molecules into membranes, which are organized structures of a higher degree of complexity than large molecules, are not yet very well understood. There is reason to believe that the incorporation of a molecule into a membrane endows it with properties that differ from those of a molecule in solution. A primary task of biophysics is to understand the physical character of these cooperative interactions that are essential to life.
Sensory communication: The above comprise a few specific examples of the scope of biophysics. One area, difficult to discuss in specific terms, is that of sensory communication. Because stimuli, particularly those of a visible or auditory nature, can easily be specified in exact physical terms, they have excited the interest of physical scientists since before 1850. Modern electronic techniques make it relatively easy to distinguish true signals from noise; in addition, computers make possible the performance of significant experiments concerning the complex relationship between stimulus and action. Quantitative analysis of sensory response is very difficult, however, because it involves a synthesis of the action of many cells.
Biophysics is the application of the principles of physics (the science that deals with matter and energy) to explain and explore the form and function of living things. The most familiar examples of the role of physics in biology are the use of lenses to correct visual defects and the use of X-rays to reveal the structure of bones.
Computerized axial tomography (CAT scan): An X-ray technique in which a three-dimensional image of a body part is put together by computer using a series of X-ray pictures taken from different angles along a straight line.
Electron microscope: A microscope that uses a beam of electrons to produce an image at very high magnification.
Laser: A device that uses the movement of atoms and molecules to produce intense light with a precisely defined wavelength.
Magnetic resonance imaging (MRI): A technique for producing computerized three-dimensional images of tissues inside the body using radio waves.
Positron-emission tomography: A technique that involves the injection of radioactive dye into the body to produce three-dimensional images of the internal tissues or organs being studied.
Ultracentrifuge: A machine that spins at an extremely high rate of speed and that is used to separate tiny particles out of solution, especially to determine their size.
X ray: A form of electromagnetic radiation with an extremely short wavelength that is produced by bombarding a metallic target with electrons in a vacuum.
X-ray diffraction: A technique for studying a crystal in which X-rays directed at it are scattered, with the resulting pattern providing information about the crystal’s structure.
Principles of physics have been used to explain some of the most basic processes in biology such as osmosis, diffusion of gases, and the function of the lens of the eye in focusing light on the retina. (Osmosis is the movement of water across a membrane from a region of higher concentration of water to an area of lower concentration of water. Diffusion of gases is the random motion of gas particles that results in their movement from a region of higher concentration to one of lower concentration.)
The understanding that living organisms obey the laws of physics – just as nonliving systems do – has had a profound influence on the study of biology. The discovery of the relationship between electricity and muscle contraction by Luigi Galvani (1737-1798), an Italian physician, initiated a field of research that continues to give information about the nature of muscle contraction and nerve impulses. Galvani’s discovery led to the development of such instruments and devices as the electrocardiograph (to record the electrical impulses that occur during heartbeats), electroencephalograph (to record brain waves), and cardiac pacemaker (to maintain normal heart rhythm).
The use of a wide array of instruments and techniques in biological studies has been advanced by discoveries in physics, especially electronics. This has helped biology to change from a science that describes the vital processes of organisms to one that analyzes them. For example, one of the most important events of this century – determining the structure of the DNA molecule – was accomplished using X-ray diffraction. This technique has also been used to determine the structure of hemoglobin, viruses, and a variety of other biological molecules and microorganisms.
Focus on the Field: While some colleges and universities have dedicated departments of biophysics, usually at the graduate level, many do not have university-level biophysics departments, instead having groups in related departments such as biochemistry, cell biology, chemistry, computer science, engineering, mathematics, medicine, molecular biology, neuroscience, pharmacology, physics, and physiology. Depending on the strengths of a department at a university differing emphasis will be given to fields of biophysics.