Biological cells are unbelievably complex machines that orchestrate thousands of different kinds of molecules simultaneously. For this, it is paramount that different parts work isolated from one another, much like in man-made machines. To achieve such spatial organization, biological cells are divided by membranes that enclose large organelles, like the nucleus, mitochondria, or the Golgi apparatus. However, cells also possess many small organelles that are not bound by membranes. Recent experiments show that these membrane-less organelles can be thought of as liquid droplets. Cells thus harness the physical process of phase separation to segregate material into different compartments.
Phase separation is a classical phenomenon in statistical physics and has been studied for more than a century. Basically, phase separation occurs when attractive interactions of like particles dominates the interactions of unlike particles, so the total free energy of the system can be lowered by concentrating like particles into different phases – the system demixes. However, the unavoidable interface between the phases still has a relative high free energy, which is also known as surface energy or surface tension. Consequently, simple equilibrium systems tend to minimize the interfacial area. In emulsions, which contain many droplets, this leads to Ostwald ripening, where large droplets grow at the expense of smaller ones, implying that only a single droplet remains in thermodynamic equilibrium. Considering this instability of multiple droplets, it is difficult to understand how cells control counts, positions, sizes, and morphologies of their membrane-less organelles.
Cells differ from classical physical systems in that they live. One hallmark of life is that a constant energy flux keeps the system away from the thermodynamic equilibrium. For example, chemical reactions involving the fuel ATP drive most cellular functions. We study how droplets are affected when the droplet material participates in such reactions. In a recent publication with coauthors from three institutions in Dresden, Germany (MPI for Physics of Complex Systems, MPI for Cell Biology and Genetics, and Technical University Dresden), we show that such active droplets exhibit diffusive fluxes even in stationary states, which itself is a hallmark of non-equilibrium systems. We also show that depending on the direction of these fluxes, solid-like particles inside the droplet can be either centered inside the droplet or expelled from it. The fluxes induced by the chemical reactions thus allow to control the morphology of active droplets. We also show that such a model can explain the structure of centrosomes, which are one example of membrane-less organelles in cells. More generally, our work shows that driving droplets with chemical reactions might allow biological cells to control droplet formation to structure their interior.