The theme of this work is to develop a useful, accurate science of forces that organize biomolecules. To this end we have concentrated our efforts t measure forces between proteins, DNA double helices, and polysaccharides. The Osmotic Stress method for direct force measurements is winning widespread use around the world. Our LSB home page contains a ~living handbook~ of osmotic stress data and calibration curves. Records indicate that our home page is sometimes accessed as often as once every couple of minutes. The latest work on DNA forces combines osmotic stress with SAXS and polarization microscopy. Use of synchrotron radiation as well as ordinary x ray sources has shown several different forms of molecular packing, including a cholesteric phase characterized by great motional freedom (dialysis experiments at low osmotic pressures extended the range of previous force measurements demonstrating a new fluctuation enhanced force regime). The remarkable feature of this motional enhancement is a quadrupling of the range of direct forces. These observations are being connected with the most sophisticated physical theories of liquid-crystal assembly as well as with immediate questions how DNA fits within the confines of small spaces such as viral capsids. Quantitative measurement of the amount of water released upon the binding o various proteins to DNA shows qualitative differences in dehydration when the protein/DNA association is specific rather than non-specific. There is an apparent connection between these changes in molecular hydration and the powerful """"""""hydration forces"""""""" measured between large molecules brought into contact. We have finally enjoyed clear progress on a major theoretical question, the annoying, """"""""vapor pressure paradox,"""""""" wherein membranes are known to imbibe less water from a vapor than from a liquid solution of the same chemical potential as water. According to our formulation, a surface that suppresse molecular motion will exert its repression very far into a medium (even cellular dimensions) and will stop molecular expansion. Within weeks of ou initial formulation, experiments suggested to another laboratory showed the kind of surface perturbation that was predicted. Other labs are now showin the generality of the phenomenon we have identified. The consequence of this work is that we must ask whether the solution properties of bilayer membranes, or ~semi-flexible~ molecules such as DNA, are the same within th micron-wide confines as they are in the centimeter-size vessels in which they are normally studied.
