 This work is dedicated to Franz Rosenberger, who has been to me a valuable guide in the field of protein crystallisation, on the occasion of his (hopefully just official) retirement. Journal of Crystal Growth 196 (1999) 415— 423 Interactions in protein solutions near crystallisation: a colloid physics approach Roberto Piazza Istituto Nazionale per la Fisica della Materia, Dipartimento di Elettronica, Universita+ di Pavia, 27100 Pavia, Italy Abstract I present a review of current ideas from colloid physics which might be relevant in order to understand the onset of crystallisation and amorphous aggregation processes in protein solution. In particular, the inadequacy of DLVO theory to account for all phenomenological aspects of crystallisation, such as salt-specificity, and for the basic features of the phase diagram, such as the presence of a metastable fluid—fluid separation, is discussed. The fundamental role of additional short-range attractive forces, microscopically orginating from the salting-out effect, is conversely stressed. In order to establish a simple model of protein interparticle interactions near crystallisation, I discuss some recent results obtained by our group for the osmotic compressibility of the metastable fluid phase of hen egg-white lysozyme. Light scattering measurements were performed in an extended volume fraction range at pH"4.7 as a function of temperature, adding NaC1 to screen the electrostatic interactions. The experimental compressibility up to particle volume fractions +0.23 is very successfully compared to the theoretical expression for a model of adhesive (“sticky”) hard spheres. This surprising quantitative agreement, obtained using a very simple form for the effective interparticle force, suggests that the thermodynamics of the system in the fluid phase is mainly determined by the very short-range nature of the interactions, and is rather insensitive to the detailed form of the potential.  1999 Elsevier Science B.V. All rights reserved. PACS: 87.15.Da; 82.70.Dd Keywords: Proteins; Colloids; Phase transitions; Light scattering; Complex fluids The last two decades have seen a steady growth of interest in colloidal fluids by the research com- munity due to advances in condensed matter phys- ics. Indeed, colloidal suspensions share in common with simple molecular systems many features of the phase diagram such as gas, liquid, solid, or even glass-like phases. But they allow in addition a con- trolled trimming of the interparticle potential, show longer relaxation times permitting to study meta- stable structures, and present structural length scales suitable to be investigated by accurate labor- atory-sized techniques like dynamic light scattering (for an excellent review, see Ref. [1]). All these 0022-0248/99/$ — see front matter  1999 Elsevier Science B.V. All rights reserved. PII: S 0 0 2 2 - 0 2 4 8 ( 9 8 ) 0 0 8 6 7 - 7