Liquid-Liquid Phase Separation Bridges Physics, Chemistry, and Biology

There is a fundamental gap between the inherent complexity of biology and the simplicity that physicists and chemists often seek. In this Perspective, we reason that liquid- liquid phase separation (LLPS) could be utilized to (partially) fill this gap and to bridge different disciplines because LLPS can produce condensed droplets with simplicity and complexity at the same time. Specifically, the droplets are often compositionally simple (made of, for example, proteins and polyelectrolytes) and structurally uniform (not so different from an oil droplet in water). Contrary to this simplicity is their functional complexity-the droplets can perform various physiological activities with subcellular precision. This spatiotemporal precision further stimulates an ongoing endeavor in the synthetic realm to develop regulatory strategies that may ultimately match or even surpass their biological counterparts. We envision the phase-separated droplets to open a window of simplicity for us to peek into the complexity of biology, and we foresee that joined forces across different disciplines would substantially advance our understanding of LLPS in biotic and abiotic contexts.