It was a truth universally acknowledged when we were younger that to implement honest thermodynamics about the real world would be just a fantasy. To attempt this would be an effective way to fail our exams, unless we chose toy models. But in two recent papers1,2, experiments and theory agree when this spirit of analysis is applied to phase separation in a generic biomolecular system. Writing in Nature Materials, Alexandra Tayar et al.1, focusing on phase boundaries, show that activity stabilizes the mixed state and narrows the coexistence concentrations. Writing in Physical Review Letters, Daniel Arnold, Aakanksha Gubbala et al.2, focusing on the kinetic side of phase separation in a related system, show that activity speeds this process up and modifies interesting power laws.

The experimental insight was to rely on the active flow of long, threadlike active agents: liquid crystalline cytoskeletal polymers. The ‘active matter’ field of modern physics describes materials whose constituent units consume energy and hence are out of equilibrium, but because the seminal ideas came from theory and computer simulation3,4,5, progress has been impeded by the paucity of experimental systems against which to test predictions rigorously. Years ago, the specific question of how activity modifies phase separation was already posed, but those studies were implemented for simpler spherical units5, which turn out not to display the physics now reported. Even earlier, researchers sheared two-phase molecular systems in search of modified critical temperatures, but the influences they discovered were small6,7. The four main components in this active-matter system are microtubules, which are micrometre-long polymers; kinesin molecular motors that walk along microtubules powered by their adenosine triphosphate (ATP) fuel; a depletion agent, polyethylene glycol; and DNA nanostars that tend to separate from the mixed state (Fig. 1). Although theory can now describe the new experiments1, earlier theorists did not anticipate that experimentalists would use the complex four-component cocktail used now1.

Fig. 1: Activity-controlled phase separation in a biomolecular system.
figure 1

a, Active motion shifts the classical phase diagram of DNA nanostars to a lower critical temperature and narrower coexistence region; temperature (T) is plotted against volume fraction (Φ) and the region of phase-separated DNA nanostars lies below each curve. b, Scheme of the mechanism: active flow of microtubules mechanically linked to DNA nanostars by molecular motors drastically deforms a hypothetical phase-separated liquid droplet of DNA nanostars.

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The theoretical analysis by Tayar et al. implicitly explains why earlier studies only found a minor influence of shear in their systems. When agitated fluid stresses only the interface, the predicted effect is minimal; it is large only when the model allows shear to propagate into the interior of phase-separating droplets. Such propagation requires the exterior and interior to be linked mechanically. This offers a promising design principle for designing future new experimental systems.

There have been arguments for and against the consideration of temperature and activity as independent variables. Thermal energy agitates all matter, so if units of energy-consuming active matter contribute extra agitation, there might exist a non-equilibrium effective temperature, different from the thermal temperature, as has been proposed to describe granular and colloidal particles8,9. On the other hand, the time scales of thermal agitation and activity differ drastically, and beyond this, actions induced by thermal energy are not coherent. In the papers by Tayar et al.1 and Arnold, Gubbala et al.2, active flow is coherent on length scales so large that they modulate long-range mechanical forces, so it may be reasonable to consider temperature and activity independently. The papers wisely sidestep these conceptual questions as they are so complex. Pragmatic readers may decide that the proof is in the pudding: to ignore them seems to work.

Despite this beautiful agreement between theory and experiment regarding thermodynamics1, the tantalizing new kinetic power laws2, and the new design principle offered by the insight of required mechanical coupling across interfaces1, the authors point out a worry. Earlier this year, others measured the efficiency of flows similar to those analysed here and concluded that much of the energy consumed by active units does not go into the viscous flow used to explain these experiments10.

Might the missing energy be relevant to some kind of alternative explanation of the experiments? Might these discoveries1,2 and the missing energy problem have bearing on understanding biological phase-separation processes in the presence of cellular metabolism? This field is advancing too quickly to answer these questions yet.