Water near intracellular surfaces.

In this paper we make the following points: Water is perturbed within several angstroms of the surfaces of soluble molecules. Removal of this water can require significant amounts of work, seen as an exponentially varying "hydration force" with respect to molecular separation. The favorable and specific attractions that occur in molecular assembly or in ligand binding imply that the specific association between the molecular surfaces is stronger than the association of those surfaces with water. The specificity of biochemical association is not simply a matter of protein-protein interaction but also of competing protein-water interactions. Small structural changes in molecular surfaces can evoke large changes in the contact energy of hydrated surfaces; surface hydration and the energetics of water displacement are a likely mechanism for the contact specificity of intracellular associations integrating the cell matrix.

Forces between lecithin bimolecular leaflets are due to a disordered surface layer.

The long-range repulsion observed between bileaflets of lecithin cannot be explained either with the usual view that the polar groups are arrayed coplanar with the bileaflet surface or by the assumption that charges protrude straight into the aqueous environment. Statistical-thermodynamic analysis of experimental data suggests rather that structure of the leaflet surface is better described as a diffuse charge layer. Forces between leaflets are caused largely by entropy changes in the surface with leaflet separation.

Direct measurement of forces between linear polysaccharides xanthan and schizophyllan.

Direct osmotic stress measurements have been made of forces between helices of xanthan, an industrially important charged polysaccharide. Exponentially decaying hydration forces, much like those already measured between lipid bilayer membranes or DNA double helices, dominate the interactions at close separation. Interactions between uncharged schizophyllans also show the same kind of hydration force seen between xanthans. In addition to the practical possibilities for modifying solution and suspension properties through recognition and control of molecular forces, there is now finally the opportunity for theorists to relate macroscopic properties of a polymer solution to the microscopic properties that underlie them.

Protein solvation in allosteric regulation: a water effect on hemoglobin.

The oxygen affinity of hemoglobin varies linearly with the chemical potential of water in the bathing medium, as seen from the osmotic effect of several neutral solutes, namely sucrose, stachyose, and two polyethyleneglycols (molecular weights of 150 and 400). The data, analyzed either by Wyman linkage equations or by Gibbs-Duhem relations, show that approximately 60 extra water molecules bind to hemoglobin during the transition from the fully deoxygenated tense (T) state to the fully oxygenated relaxed (R) state. This number, independent of the nature of the solute, agrees with the difference in water-accessible surface areas previously computed for the two conformations. The work of solvation in allosteric regulation can no longer go unrecognized.

Apparent modification of forces between lecithin bilayers.

Small sugar solutes effect variation in the equilibrium separation of lecithin bilayers in aqueous solution. Since sugars have negligible influence on bilayer structure, they probably act by modifying interbilayer forces. The observed widening and narrowing of the bilayer separation is correlated with the predicted weakening and strengthening of the attractive van der Waals forces between lipid bilayers that occurs with increasing sugar concentrations.

A phenomenological one-parameter equation of state for osmotic pressures of PEG and other neutral flexible polymers in good solvents.

We present a phenomenological one-parameter scaling equation of state that accurately represents osmotic pressures of neutral flexible polymers in good solvents from the dilute through the semidilute regime. The equation comprises a sum of scaled van't Hoff and des Cloizeaux terms including a fitted parameter alpha, the "crossover index", which encapsulates all chemical specificity and determines the relevant prefactors. Strikingly different values of alpha are found for the two very different systems poly(ethyleneglycol)/water (PEG) and poly(alpha-methylstyrene)/toluene (PAMS). Alpha-dependent rescaling collapses both data sets to a simple one-parameter scaling function. The fact that the anomalous system PEG/water and the canonical system PAMS/toluene can both be described by the same equation of state attests to the robustness of the polymer-scaling concepts introduced by de Gennes.

DNA--DNA interactions.

The forces that govern DNA double helix organization are being finally systematically measured. The non-specific longer-range interactions--such as electrostatic interactions, hydration, and fluctuation forces--that treat DNA as a featureless rod are reasonably well recognized. Recently, specific interactions--such as those controlled by condensing agents or those consequent to helical structure-are beginning to be recognized, quantified and tested.

Chemical potential measurements of deoxyhemoglobin S polymerization. Determination of the phase diagram of an assembling protein.

We have used the "osmotic stress" method to determine the phase diagram of deoxyhemoglobin S polymerization. This method involves equilibration, through a semipermeable membrane, of the protein with solutions of inert polymers of known osmotic pressure. With deoxyhemoglobin A and S solutions, in which we have demonstrated achievement of equilibrium, plots of osmotic pressure versus concentration initially agree closely with the results of other methods of measurement of colligative properties. However, once the known solubility value is exceeded for the deoxyhemoglobin S solutions at various temperatures, there is a rapid rise in hemoglobin concentration over a narrow osmotic pressure range and then a more gradual increase in concentration. We believe that these two regions correspond, respectively, to the onset of the polymerization process, and of subsequent continuing growth and compression or alignment of polymer. We derive the thermodynamic values for these processes and show that the behavior of the deoxyhemoglobin S system is analogous to the phase transition for a simple chemical system. These results are relevant to understanding the intracellular polymerization of deoxyhemoglobin S in sickle cell disease, and these concepts are applicable to other protein assembly systems.

Membrane interaction and deformation.

Membrane interaction and membrane deformation should be considered two aspects of the same phenomenon. Because membrane interaction depends on structural features such as curvature, chemical composition, and surface organization, one must expect that these features will change as membranes are brought together. Our observations on model phospholipid membranes have allowed us to measure and to distinguish electrostatic (coulombic or double-layer) forces, electrodynamic (van der Waals, dispersion) interactions, and hydration forces due to the solvation of polar groups that are stabilizing the membrane surface. As a consequence of these interactions, approaching membranes may flatten against each other, may change the packing density of their constituent molecules, may rearrange the composition of components in regions close to the apposing membrane, or may even show conformational changes in the arrangement of the lipid hydrocarbon chains. Abundant examples of such deformation accompanying membrane interaction are evident from x-ray diffraction and electron microscopic observations.

Watching molecules crowd: DNA double helices under osmotic stress.

Simultaneous measurements on the packing and energetics of high-density liquid crystalline DNA phases show that the crowding of long DNA polyelectrolytes at ever increasing concentrations is accomplished through straightening of the random coils that the double helix assumes in dilute solution. X-ray scattering by ordered phases reveals that the local straightening of the molecules is also accompanied by their progressive immobilization and confinement within the molecular 'cages' created by neighboring molecules. These effects can be clearly observed through the measured energies of DNA packing under osmotic stress and through the changes in structural and dynamic characteristics of X-ray scattering from DNA in ordered arrays at different concentrations. The character of the confinement of large DNA motions for a wide range of DNA concentrations is dominated by the soft potentials of direct interaction. We do not see the power-law variation of energy vs. volume expected from space-filling fluctuations of molecules that enjoy no interaction except the hard clash of steric repulsion. Rather, in highly concentrated DNA mesophases we see a crowding of molecules through electrostatic or hydration repulsion that confines their movements and positions. This view is based on directly measured packing energies as well as on concurrently measured structural parameters while the DNA double helices are condensed under an externally applied osmotic pressure.

Watching small molecules move: interrogating ionic channels using neutral solutes.

Whether they are small enough to wriggle through the current-carrying part of an ionic channel or big enough to be kept outside and thus able to exert an osmotic stress on the channel space, polymers interact with channels in several instructive ways. The osmotic stress of excluded polymers allows one to measure the number of water molecules that come out of the channel in transitions between various "open" to "closed" states. The loss of osmotic activity, due to the partial or completely unrestricted admission of small polymers becomes a measure of the transfer probabilities of polymers from solution to small cavities; it provides an opportunity to study polymer conformation in a perfectly sieved preparation. Current fluctuations due to the partial blockage by a transient polymer are converted into estimates of times of passage and diffusion constants of polymers in channels. These estimates show how a channel whose functional states last for milliseconds is able to average over the interactions with polymers, interactions that last only microseconds. One sees clearly that in this averaging, the macromolecular channel is large enough to react like a macroscopic object to the chemical potentials of the species that modulate its activity.

Osmotic properties of DNA: critical evaluation of counterion condensation theory.

The osmotic coefficient of B-DNA in water may, in dilute solutions, deviate by as much as 100% from predictions based on a simple line-charge "counterion condensation" theory. In contrast, a cell model description of the ionic atmosphere near a cylindrical polyelectrolyte predicts osmotic properties that are in surprisingly good harmony with all available experimental findings over a wide range of DNA concentrations. We argue that the neglect of molecular features, such as finite radius, makes line-charge condensation theory inapplicable at all but impractically low polyelectrolyte concentrations.

Forces between membranes approaching contact.

Cell stickiness to surfaces is recognized as an important concern in tests of red cell filterability. Many forces need to be considered in order to think about the sources of cell sticking. As cell membranes are brought together they experience successively the domination of several classes of forces van der Waals attraction, electrostatic repulsion, hydration repulsion, and specific charge-charge interactions at contact. The behaviour of each of these forces is described in the context of red cell adhesion.

Polymers pushing Polymers: Polymer Mixtures in Thermodynamic Equilibrium with a Pore.

We investigate polymer partitioning from polymer mixtures into nanometer size cavities by formulating an equation of state for a binary polymer mixture assuming that only one (smaller) of the two polymer components can penetrate the cavity. Deriving the partitioning equilibrium equations and solving them numerically allows us to introduce the concept of "polymers-pushing-polymers" for the action of non-penetrating polymers on the partitioning of the penetrating polymers. Polymer partitioning into a pore even within a very simple model of a binary polymer mixture is shown to depend in a complicated way on the composition of the polymer mixture and/or the pore-penetration penalty. This can lead to enhanced as well as diminished partitioning, due to two separate energy scales that we analyse in detail.

Optically anisotropic infinite cylinder above an optically anisotropic half space: Dispersion interaction of a single-walled carbon nanotube with a substrate.

A complete form of the van der Waals dispersion interaction between an infinitely long anisotropic semiconducting/insulating thin cylinder and an anisotropic half space is derived for all separations between the cylinder and the half space. The derivation proceeds from the theory of dispersion interactions between two anisotropic infinite half spaces as formulated in Phys. Rev. A 71, 042102 (2005). The approach is valid in the retarded as well as nonretarded regimes of the interaction and is coupled with the recently evaluated ab initio dielectric response functions of various semiconducting/insulating single wall carbon nanotubes, enables the authors to evaluate the strength of the van der Waals dispersion interaction for all orientation angles and separations between a thin cylindrical nanotube and the half space. The possibility of repulsive and/or nonmonotonic dispersion interactions is examined in detail.