# Phase transitions in biological systems with many components

## TL;DR

This paper demonstrates through numerical evidence that biological mixtures with many components can spontaneously phase separate into distinct regions, with the process being robust and tunable, facilitating spatial organization in cells.

## Contribution

It reveals that multicomponent biological mixtures naturally tend to undergo phase separation due to general phase diagram features, highlighting robustness and tunability of cellular compartmentalization.

## Key findings

- Demixed domains form when interaction variance exceeds a threshold.
- Multiple phases can coexist under similar conditions, tunable by composition.
- Phase separation remains robust with increasing component number.

## Abstract

Biological mixtures such as the cytosol may consist of thousands of distinct components. There is now a substantial body of evidence showing that, under physiological conditions, intracellular mixtures can phase separate into spatially distinct regions with differing compositions. In this paper we present numerical evidence indicating that such spontaneous compartmentalization exploits general features of the phase diagram of a multicomponent biomolecular mixture. In particular, we show that demixed domains are likely to segregate when the variance in the inter-molecular interaction strengths exceeds a well-defined threshold. Multiple distinct phases are likely to become stable under very similar conditions, which can then be tuned to achieve multiphase coexistence. As a result, only minor adjustments to the composition of the cytosol or the strengths of the inter-molecular interactions are needed to regulate the formation of different domains with specific compositions, implying that phase separation is a robust mechanism for creating spatial organization. We further predict that this functionality is only weakly affected by increasing the number of components in the system. Our model therefore suggests that, for purely physico-chemical reasons, biological mixtures are naturally poised to undergo a small number of demixing phase transitions.