  Most bacteriophages are known to inject their double-stranded DNA into
bacteria upon receptor binding in an essentially spontaneous way. This downhill
thermodynamic process from the intact virion toward the empty viral capsid plus
released DNA is made possible by the energy stored during active packaging of
the genome into the capsid. Only indirect measurements of this energy have been
available until now using either single-molecule or osmotic suppression
techniques. In this paper, we describe for the first time the use of isothermal
titration calorimetry to directly measure the heat released (or equivalently
the enthalpy) during DNA ejection from phage lambda, triggered in solution by a
solubilized receptor. Quantitative analyses of the results lead to the
identification of thermodynamic determinants associated with DNA ejection. The
values obtained were found to be consistent with those previously predicted by
analytical models and numerical simulations. Moreover, the results confirm the
role of DNA hydration in the energetics of genome confinement in viral capsids.
