STRUCTURE AND THERMODYNAMICS OF NONIDEAL SOLUTIONS OF COLLOIDAL PARTICLES - INVESTIGATION OF SALT-FREE SOLUTIONS OF HUMAN SERUM-ALBUMIN BY USING SMALL-ANGLE NEUTRON-SCATTERING AND MONTE-CARLO SIMULATION

The understanding of the structural and thermodynamic properties of mo derately or highly concentrated solutions is fundamental, e.g., in med icine and biology and also in many technical processes, In this work, we have used the small-angle neutron scattering method (SANS), in comb ination with Monte Carlo simulation, to study salt-free solutions of h uman serum albumin (HSA) in the concentration range up to 0.26 g ml(-1 ). The model calculations of the theoretical SANS intensities are quit e general, thus avoiding the approximation that the relative positions and orientations of the particles are independent of each other. The computation of the theoretical intensities also includes the calculati on of a 'thermodynamic' intensity scattered at zero angle, which is ob tained via the nonideal part of the chemical potential. The latter qua ntity is obtained by applying the test particle method during the Mont e Carlo simulations. It is found that the SANS data can be explained b y a model where the HSA molecules behave as hard ellipsoids of revolut ion with semiaxes a = 6.8 nm, b = c = 1.9 nm. In addition to the hard core interaction, the particles are also surrounded by a soft, repulsi ve rectangular-shaped potential which is spherically oriented around t he particles. The combination of SANS and statistical thermodynamics a lso allows a determination of the nonideal part of the chemical potent ial and the activity coefficient of HSA. As expected the activity coef ficient deviates strongly from the value one (several powers of ten) a lready at fairly low concentrations; the effects are comparable to, or even larger than, for instance hydrophobic or van der Waals interacti on. (C) 1997 Elsevier Science B.V.