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DOI: 10.1201/9781003336433-6

6

Forces

Methods that Measure and/​or Manipulate

Biological Forces or Use Forces in

Their Principal Mode of Operation on

Biological Matter

What would happen if we could arrange the atoms one by one the way we want them?

—​Richard Feynman, Physicist (1959)

General Idea: Several biophysical methods can both measure and manipulate biological forces

across a range of length and time scales. These include methods that characterize forces in

whole tissues, down through to single cells and to structures inside cells, right down to the

single-​molecule level. The force fields that are generated to probe the biological forces originate

from various sources including hydrodynamic drag effects, solution pressure gradients, elec­

trical attraction and repulsion, molecular forces, magnetism, optical forces, and mechanical

forces. All of which are explored in this chapter.

6.1  INTRODUCTION

All experimental biophysical techniques clearly involve measurement and application of

forces in some form or another. However, there is a subset of methods that are designed

specifically to either measure the forces generated in biological systems, or to control and

manipulate them. Similarly, there are tools that do not characterize biological forces directly,

but which primarily utilize force methods in their mode of operation, for example, in using

pressure gradients to purify biomolecular components.

There now exist several methods that permit both highly controlled measurement and

manipulation of the forces experienced by single biomolecules. These various tools all come

under the banner of force transduction devices; they convert the mechanical molecular

forces into some form of amplified, measurable signal. Many of these single-​molecule force

techniques share several common features, for example, single molecules are not in general

manipulated directly but are in effect physically conjugated, usually via one or more chemical

links, to some form of adapter that is the real force transduction element in the system. The

principal forces that are used to manipulate the relevant adapter include optical, magnetic,

electrical, and mechanical. These are all coupled into an environment of complex feedback

electronics and stable, noise-​minimizing microscope stages, both for purposes of measure­

ment and for manipulation.

Single-​molecule biophysics methods extend beyond just force tools, which we explore

here, encompassing also a range of advanced imaging techniques that we explored previously