Chapter 1 – Introduction  7

be needed… the point here is that biology at the molecular scale often works

on small nanoscale level fluctuations as opposed to making dramatic changes

orders of magnitude higher…

c

I wonder what speculations you came up with! The real reason is that DNA is not

actually a Hookean spring; it only appears to be over relatively short stretches. For

longer stretches, DNA behaves non-​linearly, so that the force is no longer directly

proportional to the end-​to-​end extension of the molecule, and it instead behaves,

like many such filamentous polymers, as something called an “entropic spring”

(see Chapter 8) such that when the end-​to-​end extension approaches the fully

extended length of the molecule (also known as the contour length), then the

spring force of molecular retraction becomes, in principle, infinitely high (at least

until the chemical bonds that link the polymer together themselves are broken)

since it only has one conformation to adopt (i.e., very ordered) as opposed to at

lower extensions (i.e., very disordered), which is a driving entropic force working

to retract an extended molecule like DNA back to its relaxed state. This means

that you can never completely extend the DNA molecule fully (it would take an

infinite amount of energy…) and so the DNA spring force in practice will keep on

increasing as the molecule is extended by the two optically trapped beads until

the maximum trapping force is reached at which point either bead is at the very

end of their respective optical trap and thermal fluctuations are sufficient to allow

one of the beads to simply escape out of the trap.

1.2  WHAT DO WE MEAN BY A “TOOLBOX?”

There are some notable differences between the core strategy of scientific research between

physics and biology. Research in the life sciences, in its modern form, is very much optimized

toward hypothesis-​driven research. This means, in essence, setting out theories as models of

scientific phenomena and constructing empirical investigations that can falsify these hypoth­

eses (for interested readers in this basic area of the scientific method, see Popper, 1963),

though can never actually prove them. To many scientists, this approach is simply what

science is all about and is simply what separates science from pseudoscience. But a potential

issue lies in investigating the phenomena that are currently undertheorized, to the extent

that one can ask key scientific questions that are testable; but this is not necessarily the same

as a “hypothesis” that a biologist might construct, which often involves an elaborate existing

theory from that particular area of the life sciences. Many of these undertheorized areas

are relevant to physics research, involving fundamental physical phenomena as opposed to

the “fine-​tuning” details of different aspects of testable existing model, and might better be

described as exploratory-​driven research. I mention this here simply to forewarn the reader

of the differences in perception of what constitutes “good science” by some biologists and

some physicists, since this, hopefully, will assist in a better genuine communication of scien­

tific concepts and research between the two sciences.

A key challenge to finding answers in the biological sciences is the trick of knowing the

right questions to ask. Physical science techniques applied to the life sciences, whether

experimental or analytical, have often arisen from the need to address highly focused and

specific questions. However, these techniques in general have capabilities to address a range

of different questions in biology, not necessarily related to the biological systems of the ori­

ginal questions. As such, new emerging questions can be addressed by applying a repertoire

of dynamically emerging physical tools, and this repertoire of physical science tools is essen­

tially a “toolbox.” But as any master craftsman knows, of key importance with any toolbox is

knowing which are the best tools for the job in hand.

Not only knowing what are the right questions to ask but also knowing what are the best

modern physical science tools to address these questions can, in all but exceptional cases, be

difficult to address simultaneously. The former is the realm of the expert biologist in an often