Cluster formation in binary mixtures of self-assembling fluids as a model of internal phase segregation in biological condensates

Cytosol is a biological mixture of distinct components and under different physiological conditions it may phase separate into regions with distinct compositions. Some of these regions can condensate showing a higher density of nucleic acids and proteins. Thes biological condensates, with a size around 0.2-2µm, are observable with fluorescence confocal microscopy and electron microscopy. Membraneless organelles (MLO) are dense liquid droplets that emerge in these condensates and are responsible for different cellular functions such as signaling or gene regulation among others. In particular, RNA-binding protein TDP-43 forms aggregates that can undergo an internal phase separation with a fibrilization at the surface of the condensate associated with several neurodegenerative diseases. Our goal is to unveil what is causing the segregation to occur at the surface by modeling the phase separation within the droplets. We have used a SALR potential based on the two-exponential model to generate clusters of a desired diameter in an asymmetric binary mixture. With the right range and intensity of the cross-interaction, we have found that the B component segregates in clusters at the surface of each droplet, resembling the biological system of RNA-binding protein TDP-43.