In order to asses the interactions between biological macromolecules one would like to measure the osmotic pressure in ordered arrays of these molecules. From osmotic pressure it is possible to extract the underlying interactions potential via standard methods of statistical thermodynamics.

But how does one measure the osmotic pressure in macromolecular arrays? One possibility is to do a Boyle experiment, i.e. compressing the macromolecular subphase mechanically.

This experiment is however difficult to do because of the mechanical weakness of the semipermeable membranes. A far better option is to exploit chemical equilibrium of the macromolecular subphase with a subphase of known osmotic pressure. The polymer ion this subphase can be e.g. PEG (polyethylene glycole or polyethylene oxide) for which the osmotic pressure as a function of concentration has been studied extensively.

By varyingthe osmotic pressure of the PEG subphase and concurrently measuring the density of the macromolecular subphase one gets an equation of state of the macromolecular subphase, i.e. the osmotic pressure as a function of density of the macromolecular subphase.

This is the essence of the s.c. osmotic stress method. At its center is the equivalence of the mechanical work (osmotic pressure) needed to bring macromolecules closer in spite of the interactions between them, and the chemical work (removing of the solute, in this case water) needed to concentrate the macromolecular subphase.

With osmotic stress method one can get equations of state, i.e. the dependence of osmotic pressure on macromolecular density, for a large variety of different macromolecules. The equation of state for DNA is the most complete example of this method in action.

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