To cope with the harsh and stressful environment, to maintain their form and integrity, biological cells have devised throughout evolution an array of effective countermeasures. Osmotic stress from the outside is counterbalanced by "osmolytes": a series of small, charges or polar (yet net-natural) solutes that balance the stress and allows the cell interior to continue to function with no serious consequences.

A delicate balance of forces is at action, as osmolytes interact with large macromolecules and affect their interaction with each other. How does the cell control the action of its osmolytes, and how do the those counteract the effects of the ions that usually compose most of the cell's osmotic environment? As we try to answer these questions, we also learn about the way the solutes interact with the macromolecules to affect their stability. First, we must be able to isolate the effect of osmolytes. This has prompted us to study the effect of cosolutes on cyclodextrin with adamantine carboxylic acid. 

Using Isothermal Titration Calorimetry and Vapor Pressure Osmometry, we have followed the complexation of cyclodextrin and adamantane in the presence of various solutes, both charged (salts) and net-neutral (polar). The response of binding to osmotic pressure indicates a release of 15-25 water molecules upon complex formation. Cosolute addition is found to significantly affect the heats of reaction. The number of released waters depends on the cosolute used, yet for many cosolutes this number correlates well with surface tensions at the air-water interface. These results indicate that different cosolutes are interacting differently with the waters at the interfaces of the non-polar "hydrophobic" complexing molecules. We discuss these findings as related to theoretical models and molecular dynamic simulations of analogous systems to learn about the ordering of water at macromolecular interfaces.

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