From the classical colloidal theory to biomolecular condensation: implications in health and disease

Abstract

Biomolecular phase separation and condensation are fundamental mechanisms of cellular compartmentalization that regulate biochemical processes in space and time. From a biophysical standpoint, biomolecular condensates can be considered biological colloids that share key properties with classical colloidal systems. In this article, we integrate classical colloidal theory with recent advances in biomolecular condensation to exemplify how physicochemical parameters, including pH, ionic strength, metal ions, and post-translational modifications, modulate the assembly dynamics and material properties of biomolecular condensates under physiological and pathological conditions. Additionally, we highlight the relationship between phase separation and amyloid formation, emphasizing recent evidence that amyloid-promoting proteins can exhibit catalytic activity in condensed or aggregated states. This perspective redefines biomolecular condensation and amyloid formation as highly versatile processes with significant implications for cell biology, disease mechanisms, and therapies.