Endogenous flow and dialytaxis govern aging of Adenosine 5'-triphosphate (ATP) condensates

Abstract

Biomolecular condensates are increasingly recognized as pivotal regulators of cellular physiology, yet their pathological aging underlies numerous diseases. However, the mechanisms governing this condensate aging remain largely elusive. Liquid-liquid phase separation of minimal biomolecular building blocks, such as small peptides or nucleotides, offers ideal model systems to dissect the mechanisms underlying condensate formation and aging. Here, we report that condensates formed by Adenosine 5-triphosphate (ATP) undergo liquid-to-solid phase transitions (LSPT) in macromolecularly crowded environments, evolving from dynamic liquid droplets into urchin-like fibrillar aggregates. In the initial stages of aging, small aggregates actively engulf surrounding droplets via direct contact and rapid wetting-driven merging. As aging progresses, internal flows emerge within condensates, with velocities oriented toward the nearest aggregate core. These flows arise endogenously from ATP fibrillization through the Marangoni effect and result in a long-range chemotaxis ripening process that facilitates transport of ATP molecules from peripheral droplets to a central aggregate. The Marangoni effect also drives the long-range motion of liquid droplets on hydrophobic surfaces towards the aggregates, representing a novel form of dialytaxis. These findings provide crucial and previously unrecognized dynamic behaviors and insights into the physical principles underlying condensate aging.