Goldfarb D. Biophysics DeMYSTiFied
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22 Biophysics D emystifieD
obstacles along the way. These factors all affect the ball’s path, and through the
path, they affect how fast it will roll down the hill.
If a process goes through intermediate steps along the way from its start to its
end and one or more intermediate steps are higher in energy (for example, rolling
up a speed bump), these are called high-energy intermediates. The presence of
high-energy intermediates, like speed bumps, tends to slow a process down. One
example of this is DNA replication, discussed in Chapter 10. In order to replicate,
the DNA double helix needs to unwind temporarily. This is a higher energy state
for the DNA. Once it is replicated, the DNA goes back to its double helical state,
which is a lower energy state. Thus, the unwound double helix is the high-energy
intermediate in the process of DNA replication.
Living systems often regulate their biological processes by modulating the
rate at which they happen. This means that, sometimes, when a living thing
needs a process to stop (for example, it already has manufactured enough of a
certain type of protein and for the time being it doesn’t need anymore), then
instead of actually stopping the process it simply allows the process to slow
down almost to a halt. The process is still happening, but at such a slow rate
that it doesn’t make much of a difference. Then, when the organism needs the
process to continue (for example, it now needs more of the protein), it simply
speeds up the rate at which the process is happening.
When an organism needs to modulate the rate at which a process happens,
typically this is done in one of two ways: either by providing the energy needed
to get over a speed bump (high-energy intermediate) or by providing an alterna-
tive path (effectively removing or going around the speed bump). Sometimes a
faster path (one without a speed bump) is provided by a conformational transi-
tion, by ligand binding, or by the binding of proteins acting as catalysts. Taking
the example again of DNA unwinding, the unwound DNA is a high-energy
intermediate, like a speed bump. A protein called helicase binds to the DNA and
unwinds the double helix. In part, the binding energy contributes to the energy
needed to attain the high-energy intermediate (the unwound DNA).
still struggling
To better understand how an energy path affects the rate of a process, consider
walking over a large hill versus walking around it. The end result is the same, you
are on the other side of the hill, but the path is different. You might think going
?
chapter 2 Biophysical Topics 23
Biophysicists studying kinetics also develop models to describe the molecu-
lar mechanism of a process. This is similar to the use of models in statistical
thermodynamics, we have discussed. The model is a hypothesis as to what the
molecular mechanism is that causes some process. Each possible model implies
a particular energy path for the process. The model may also suggest or imply
a means for changing the reaction rate, by modifying various conditions of the
experiment in a way that would alter some part of the mechanism in a known
way. Experiments measuring the rates of biological processes under various
conditions can then either support or refute the model. If the rate is success-
fully altered as the model suggests, this lends support to the correctness of the
model. If not, then the model is proven wrong, and we need to come up with
a better model to explain the process. In this way we can arrive at a molecular
interpretation of a biological process by measuring the rate of that process.
over a hill is faster than going around it, especially if you’ve got enough energy
to easily hike over the hill, since going over a hill is often shorter than going
around it. however, biological processes typically involve hundreds or thou-
sands of molecules. For example, when a cell needs to manufacture a certain
protein, it connects together hundreds of smaller molecules to make the pro-
tein. In addition to this, the cell typically needs to make hundreds or even thou-
sands of copies of the protein. So to make our analogy complete, let’s say 1000
people need to hike over the hill (or around it). The time it takes to get all 1000
people over the hill can be very slow if only some of the people have enough
energy to hike over the hill. (The others are tired and hungry.) Let’s also say there
is a tall fence alongside the path, so the only way to the other side is to go over
the hill. We have two choices to speed up the process of getting 1000 people to
the other side of the hill. We can either provide the energy they need to get over
the hill (carry them, or feed them), or we can remove the fence (a conformational
change) and provide an alternative path around the hill. in a cell, molecules are
all jostling about with various amounts of energy. if a biophysical process
involves an energy path via a high-energy intermediate, then the process will
proceed slowly if only some of the molecules have enough energy to reach the
intermediate state. in order to speed up the process, the organism either must
somehow provide the energy to get more molecules to the high-energy inter-
mediate, or it must provide an alternative path to the end of the process (a path
that does not involve a high-energy intermediate) so that even the low-energy
molecules can participate.
24 Biophysics DemystifieD
Molecular Machines
A machine is a device that can alter the direction and/or size of a force (for
example, a pulley, a lever, or an inclined plane). A motor is a special type of
machine that also has the ability to convert potential energy into mechanical
energy, that is, into a mechanical force or motion. So the difference between an
ordinary machine and a motor is that, in the case of a motor, the force being
changed does not come from outside the machine, but is generated by the
machine (the motor) itself. The motor can continue to generate mechanical
force as long as it has a source of potential energy or fuel needed to do so.
Living things are full of machines and motors. For example, our muscles use
our bones as levers to redirect and in some cases magnify or decrease the forces
they apply. Muscles themselves are motors; muscle fibers have the ability to
convert chemical potential energy from the food we eat into the mechanical
force of muscle contraction. Other examples, besides muscle contraction, of
organisms generating a mechanical force or motion include
Cilia
• . These are hairlike projections on the surface of some cells that move,
allowing the cell to swim. Or in the case of cells that don’t swim but have
cilia, the motion of cilia can be used to push substances past the cells. For
example, cilia on the inner surface cells of the lungs help clean the lungs
by moving dust and other particles up and out of the lungs.
Flagella.
• These are longer, whiplike structures that stick out from the body
of some cells and move to propel the cell forward.
Pseudopodia.
• Some cells move by temporarily pushing out on their mem-
brane at one or more locations, changing the shape of the cell and causing
the cell to crawl along.
Secretions.
• Cells that manufacture proteins or other substances to be used
elsewhere in the body (for example, pancreatic cells that manufacture
insulin) must somehow move the manufactured molecules from inside
each of the cells where they are made, to the cell’s surface, and through
the cell membrane into the bloodstream. Secretory cells have various
mechanisms for packaging and moving the substances they make.
Separation of chromosomes (DNA) during cell division.
• When a cell is get-
ting ready to divide, it first duplicates its chromosomes. The cell then has
to somehow move and separate the two copies of the chromosomes off to
two opposite sides of the cell so that the two daughter cells each get a
single copy of the cell’s DNA.
chapter 2 Biophysical Topics 25
Figure 2-5 • Bacteria use flagella to swim. Flagella are whiplike projections that
propel the cell forward. Each flagellum is a molecular machine embedded in the cell
membrane. (Courtesy of Wikimedia Commons.)
26 Biophysics DemystifieD
In all cases where organisms generate motion, a close inspection of the source
of that motion always comes down to individual molecules acting as motors and
machines in order to generate and direct forces. For example, the motion gener-
ated by muscle contraction, at the lowest level, results from individual mole-
cules of one protein (myosin) binding to and pushing against the molecules of
another protein (actin).
Allosterics
Often we find that binding in one part of a molecule affects activity in another
part of the same molecule. This property is known as allostery (from the Greek
allos meaning “other” and stereos meaning “object” or “solid object”). Allostery
allows two things to take place: allosteric regulation and cooperativity.
The control of a biological process by a cell or organism is called regulation.
In many biochemical processes, one particular part of a protein molecule is
directly involved in carrying out that protein’s function (see also the section
Structure Function Relationships ). That part is known as the active site of the
protein. Many biological processes involve binding or some other interaction
between molecules at the active site. Regulation of the process usually happens
simply by controlling binding directly at the molecule’s active site.
Sometimes regulation of a process is achieved through binding somewhere
other than the active site. This other binding site is called the allosteric site because
of its long-distance effect on the active site. When a biochemical process is con-
trolled in this way, we say that the process exhibits allosteric regulation.
Sometimes some sites behave as active sites and as allosteric sites at the same
time, each affecting the other. The result is cooperativity, the occurrence of sepa-
rate events together in a nonindependent manner. There are different degrees
of cooperativity. In a slightly cooperative process, events occur only slightly
more together than they would if they were completely independent. In a
highly cooperative process, a set of otherwise independent events occurs in a
mostly all-or-none manner.
The classic case of allosteric cooperative binding is that of oxygen binding to
hemoglobin. Hemoglobin carries oxygen from our lungs through our blood to
cells throughout our body. One hemoglobin complex can bind four oxygen
molecules. The four sites that actively bind oxygen also act as allosteric sites, each
enhancing the binding of oxygen to the remaining sites. The result is that four
oxygen molecules tend to bind to hemoglobin in an almost all-or-none manner.
The long-distance effects of an allosteric site on another part of a molecule
can be the result of conformational changes or of changes in intramolecular
chapter 2 Biophysical Topics 27
forces within the molecule. Allosteric processes typically show kinetics (changes
in rate as a response to changes in conditions) that are different from the kinet-
ics of nonallosteric processes. Biophysicists studying allosterics need to bring
together several branches of biophysics, including structure, structure-function
relationships, conformational transitions, ligand and intermolecular binding,
and kinetics.
Physiological and Anatomical Biophysics
Biomechanics
In physics, mechanics deals with the application of forces to physical objects.
The objects can be solids or fluids. For example, understanding how air flows
around an airplane wing involves mechanics, as does understanding the path of
a baseball when struck with a bat.
Biomechanics is the branch of biophysics that deals with the application of
forces to biological objects. Biomechanics includes studying such things as
The motion of animals
• . How animals apply forces to move. For example,
how muscles and bones work together in walking, running, jumping, lift-
ing, throwing, catching, and so on
The mechanics of various systems within the body.
• For example, how air is
drawn into the lungs, and how blood is pumped through the heart and
throughout the body
Mechanics at a cellular and subcellular level
• . For example, how cells move
molecules around in their interior, and how cells respond to external forces
Biomechanics is obviously a very broad subject, having considerable overlap
with many areas of biophysics. Notice also that biomechanics is studied at all
levels: subcellular, physiological, and environmental. Over the years biome-
chanics has developed into somewhat of a discipline of its own (for which we
could write Biomechanics Demystified). Thus, to some people, biomechanics
is not so much a branch of biophysics but an engineering discipline geared
toward the application of practical results. In this sense, biomechanics may be
more closely related to bioengineering or biomedical engineering than biophys-
ics. In practice, however, there are scientists who call themselves bioengineers,
and scientists who call themselves biophysicists, and both use and study biome-
chanics. But there is a tendency that the field of biomechanics is more com-
monly found in the purview of the engineers.
28 Biophysics DemystifieD
Electrophysiology
Electrophysiology is the study of electrical aspects of living things. A primary
focus of this branch of biophysics is the study of nerves. More generally though,
electrophysiology is concerned with excitable tissue, that is, cell types that cre-
ate, conduct, or use electrical impulses. Excitable tissues include nerves, mus-
cles, sensory cells, and electrogenic and electroreceptive cells.
Sensory cells are specialized cells that are able to convert energy from some out-
side stimulus into an electrical response. For example, rod cells and cone cells of the
eye contain proteins that can absorb light. The energy from the absorbed light causes
a conformational change in the protein, allowing it to react with other molecules in
the cell. This in turn starts a chain of events, resulting in an electrical charge on the
surface of the cell. Similarly hair cells in the ear contain tiny hairlike projections on
their surface. Sound vibrations in the air create pressure that pushes against these
hairs, moving them. The movement causes these cells also to generate an electrical
charge on their surface. An electrical charge on the surface of sensory cells typically
stimulates electrical impulses in neighboring nerve cells. The end result is a sensory
perception: we see light, we hear sound, we feel pressure, and so on.
Electrogenic and electroreceptive cells are found in certain electric fish such as eels
and rays. Electroreceptive cells are specialized sensory cells that create a nerve impulse
in response to an electric field. Some fish use electroreceptive cells to navigate. Elec-
trogenic cells are similar to muscle cells. However, instead of generating contraction
or movement, electrogenic cells build up strong electric charges on their surface.
Electric fish use these strong electric charges for hunting and self-defense.
Electrophysiology includes
Studying the workings of excitable tissue. For example, understanding the
•
mechanisms of contraction in muscle cells, or exploring how various con-
ditions affect the speed and strength of electrical impulses in nerves
Understanding the electrical nature of the heart, and how to measure and
•
regulate a steady pumping rhythm
Studying, at a molecular level, how cell membranes of excitable tissues
•
create electrical charges on their surfaces and propagate electrical impulses
along the length of the cell
Cable theory, using mathematics to model conduction of electrical
•
impulses along nerves and along the detailed networks of nerve cells
Investigating the mechanisms of various diseases that affect the ability of
•
nerves or muscles to work
chapter 2 Biophysical Topics 29
Sensory Biophysics
Sensory biophysics explores the electrophysiology and mechanics of the senses:
seeing, hearing, touch, balance, smell, and taste. Take vision for example. Sen-
sory biophysics explores questions such as how proteins in the eye respond to
different energies of light, how electrical signals from the retina are transmitted
to the brain, and how the eye muscles move the eye, focus the eye, and adjust
the amount of light entering the eye.
Sensory biophysics also includes research to develop artificial sensory organs,
for example, hooking a camera up to the optic nerve or to the visual cortex of
the brain so that a blind person can see. A cochlear implant is a similar device
but for sound. The implant does not amplify sound, but rather detects sound
and stimulates the auditory nerves in response to that sound.
environmental Biophysics
Environmental biophysics focuses on the physical aspects of the relationship
between the organisms and their environment. Of particular importance is the
understanding of the natural flow of energy in the environment and factors that
can affect that flow. The primary source of energy in the environment is solar
energy, which is captured through the process of photosynthesis and converted
by plants into food. There are other areas of focus within environmental bio-
physics as well.
Heat and Temperature Environmental Biophysics
This branch of environmental biophysics studies factors that control the avail-
ability of thermal energy (heat) within the environment. In this context, heat
is measured as the temperature of the atmosphere, soil, and bodies of water
(rivers, lakes, ponds, streams, and oceans). Organisms need thermal energy to
function properly. Also, the availability and movement of heat within an envi-
ronment has a strong influence on many processes happening in that environ-
ment. Those processes in turn affect the environment and the organisms within
it. The effect of temperature on organisms and their environment is also studied
within this branch of biophysics, including how organisms deal with excess
heat, or lack of heat, and how organisms themselves affect local environmental
temperatures (for example, the effects of leaf canopies on local forest tempera-
ture and the effects of microorganisms on soil temperature). Mathematical
modeling is used to predict temperatures and their effects.
30 Biophysics De mystifieD
Resource and Mass Exchange Environmental Biophysics
Environment biophysicists use mathematical models to better understand the phys-
ical movement and availability of resources and materials within the environment.
Examples of resources include heat (as just discussed), light, carbon, nitrogen, water,
and air. Take, for example, carbon. Photosynthesis captures not only solar energy but
carbon as well. Carbon is needed by all organisms. Plants capture carbon through
photosynthesis, and animals get their carbon by eating plants or other animals.
Radiation Biophysics
Radiation biophysics studies the effects of radiation on biological systems. As a
branch of biophysics, radiation biophysics can include the use of radiation in
diagnostic imaging and treatment of diseases. Such uses of radiation typically fall
under the category of imaging and medical biophysics. Within the context of
environmental biophysics, however, radiation biophysics studies how organisms
deal with radiation in their environments. Sources of radiation can be natural (for
example, solar radiation) or human-made (for example, nuclear waste). Radiation
can have a variety of effects on organisms and their environment. Solar radiation
is the primary source of energy for living things, and also has an impact on the
flow of heat, air, and water within the environment. Ultraviolet and other types
of natural and human-made radiation can cause molecular damage. Most organ-
isms have natural repair mechanisms that can often, but not always, repair dam-
age to their cells. While unrepaired damage is often trivial, it can also result in
positive mutations, as well as lethal tumors or adverse mutations.
Environmental Bioengineering
The engineering side of environmental biophysics includes
Development of sensors to detect or measure various aspects of the envi-
•
ronment
Research and development of energy-saving materials and techniques
•
Development of materials with little or no environmental impact•
Development of physical tools and techniques to counteract the negative •
environmental effects of various human activities
Research and development into low-cost methods of recycling materials
•
such as glass, metals, and plastics
chapter 2 Biophysical Topics 31
Putting it All Together
Figure 2-6 summarizes the topics discussed in this chapter. You should study
the figure to know the names of the topics and how they are categorized.
Some topics fall into more than one division. For example, bioenergetics and
biomechanics can both be studied at any level: subcellular, physiological, or
environmental.
Many topics interact with each other and to some extent overlap. Here are
some examples.
Understanding conformational transitions requires a thorough under-
•
standing of molecular structure.
The forces involved in ligand and molecular binding are the same types of
•
forces that bind together different parts of a single molecule when the
molecule folds up to take on a particular shape.
Summary of Biophysical Topics Categorized by Size of Subject
• Molecular and Subcellular Biophysics
o The Structure and Conformation of Biological Molecules
o Structure Function Relationships
o Conformational Transitions
o Ligand Binding and Intermolecular Binding
o Diffusion and Molecular Transport
o Membrane Biophysics
o DNA and Nucleic Acid Biophysics
o Protein Biophysics
o Energy Flow and Bioenergetics
o Thermodynamics
o Statistical Mechanics
o Kinetics
o Molecular Machines
o Allosterics
• Physiological and Anatomical Biophysics
o Biomechanics
o Electrophysiology
o Sensory Biophysics
• Environmental Biophysics
o Heat and Temperature Environmental Biophysics
o Resource and Mass Exchange Environmental Biophysics
o Radiation Biophysics
o Environmental Bioengineering
Figure 2-6 • Summary of biophysical topics categorized by size of
subject.