Dynamic principles of concentration buffering through liquid-liquid phase separation

Area of Science:

• Biophysics
• Cell Biology
• Biochemistry

Background:

• Living systems require stable biochemical function amidst environmental fluctuations.
• Biomolecular condensates, formed via liquid-liquid phase separation (LLPS), are known to buffer concentration changes, but their dynamic regulation is not fully understood.

Purpose of the Study:

• To systematically analyze the frequency-dependent concentration buffering capabilities of biomolecular condensates.
• To elucidate the principles governing the dynamic regulation of LLPS in response to oscillatory perturbations.

Main Methods:

• Frequency-domain analysis of LLPS response to oscillatory perturbations.
• Quantitative assessment of concentration buffering across various timescales.
• Investigation of the influence of LLPS parameters (interaction strength, droplet size, exchange rates) on buffering capacity.

Main Results:

• Biomolecular condensates function as frequency-selective filters.
• The dilute phase acts as a high-pass filter, while the dense phase attenuates both low and high frequencies.
• Established quantitative relationships between LLPS parameters and the effective buffering timescale.

Conclusions:

• LLPS provides fundamental dynamical limits for concentration buffering in biological systems.
• Findings have implications for cellular adaptation to fluctuating environments and the design of synthetic condensates.