Micro-heterogeneity and aggregation in β₂-microglobulin solutions: Effects of temperature, pH, and conformational variant addition

We show that β₂-microglobulin solutions in physiological conditions contain a tiny fraction of aggregates, which can hardly be filtered out and tend to re-form spontaneously. At physiological pH the fractional amount and size distribution of the latter aggregates do not depend on temperature. Conversely, in the pH range typical of the peri-articular tissue acidosis that often occurs in hemodialysis, temperature increase leads to fast and irreversible growth of the aggregates. Quite similar, but strongly enhanced aggregation effects can be induced even in physiological conditions by adding a very small amount of ΔN6, a naturally occurring truncated isoform of β₂-m known to promote fibrillogenesis.