Chapter 1 – Introduction  3

physics started around the middle of twentieth century, at a time when several researchers

trained originally from a background of the physical sciences made significant advances

toward the development of what we now call molecular biology. Biophysics as a new dis­

cipline was shaped significantly from the combined successes of physiology and structural

biology at around the same time. The former involved, for example, the pioneering work

of Alan Hodgkin and Andrew Huxley, which revealed how the fundamental mechanism of

conduction of sensory signals in nerves is achieved (Hodgkin and Huxley, 1952). The latter

applied emerging physics tools to study the scattering of x-​rays from crystals made of bio­

logical molecules, first exemplified in the work, from the 1930s onward, of one of the great

women of modern science, Dorothy Hodgkin (née Crowfoot), in her determination of the

structures of a number of biologically important small molecules, including cholesterol,

penicillin, and vitamin B12, but then later on much larger molecules called proteins, first

shown on one found in muscles called myoglobin (Kendrew et al., 1958).

Hodgkin and Huxley’s seminal paper, at the time of my writing this sentence, has been

cited over 16,000 times and deserves its place as one of the pioneering publications of

modern biophysics. To some biomathematicians and physiologists, this might seem contro­

versial, since they may claim this paper as one from their own fields, especially since neither

Hodgkin nor Huxley necessarily identified as being a “physicist” (their respective areas of

primary expertise were biochemistry and physiology, respectively). But with the wisdom of

historical hindsight, it is clear that their work sits very much at the cutting-​edge interdiscip­

linary interface between biology and physics.

The beauty of this exemplar study, in particular, is that it used multiple biophysical tools

to solve a challenging biological question. It investigated the fundamental properties of elec­

trical nerve conduction by reducing the problem to being one of the ion channels in cell

membranes (Figure 1.1a) that could be characterized by experimental measurements using

biophysical technology of time-​resolved voltage signals by electrodes placed inside and out­

side the nerve fiber during a stimulated nerve conduction (Figure 1.1b). But these experi­

mental signals could then be modeled using the physics of electrical circuitry (Figure 1.1c),

for example, by modeling the electric current due to ions flowing through an ion channel

in the cell membrane as being equivalent to a resistor in a standard electrical circuit, with a

voltage applied across it, which is equivalent to the voltage across the cell membrane, that is,

the difference in electrical potential per unit charge between the inside of the cell and the out­

side of the cell, denoted by Vm, and the cell membrane acting as a dielectric, thus functioning

as a capacitor (discussed in Chapter 2), here of capacitance per unit area Cm. In its simplest

form, the electric current flow I across the cell membrane can be modeled mathematically

as simply

(1.1)

I

C

V

t

I

=

+

m

m

i

d

d

where Ii is the electric current flow through the actual ion channel. This model can be

easily expanded using multiple sets of differential equations to account for multiple different

ion channels (Figure 1.1d), and this also fits the experimental observations very well.

However, the point here of these two approaches is that they illustrate not just the

achievements of new biological insight made with physical science experimental tools

and that they were both coupled closely to advances in methods of physical science analysis

techniques, in the case of nerve conduction to a coupled series of analytical differential

equations called the “Hodgkin–​Huxley model,” which describes the physics of the propaga­

tion of information in the nerves via electrical conduction of sodium and potassium ions

across the nerves’ outer electrically insulating membranes, an electric phenomenon known

by biologists as the “action potential.” X-​ray crystallography, the analysis concerned with

building mathematical tools that could in essence generate the inverse of the x-​ray scatter

pattern produced by protein crystals to reveal the underlying spatial coordinates of the con­

stituent atoms in the protein molecule, is a process involving Fourier transformation coupled

with additional mathematical techniques for resolving the phase relationship between the