Regulation of Biomolecular Phase Separation by Concentration Changes

Cells can manipulate a number of physicochemical condition parameters to construct and maintain biomolecular condensates with defined properties, such as the concentration, solubility, affinity, or valence of biomolecules. Changes in protein concentration can be caused by transcriptional bursts or the release of proteins from the reservoir. CD BioSciences offers professional services to analyze the regulation of biomolecular phase separation by concentration changes.

Introduction

The liquid-liquid phase separation (LLPS) of biomolecular condensates is driven by multivalent interactions between proteins and nucleic acids. Phase transition is a well-known process that occurs spontaneously when the concentration of a component reaches a certain threshold and is ubiquitous and plays an important role within living cells. Importantly, whether phase separation occurs depends strongly on the concentration and properties of the macromolecular solution, as well as on environmental conditions, including temperature, salt type and concentration, co-solubles, pH, and the volume repelled by other macromolecules. It has been shown that RNA in the nucleus can dynamically regulate the phase separation behavior of transcriptional complexes using a non-equilibrium feedback control mechanism in which the concentration of RNA varies with the transcriptional process.

Fig. 1. Protein phase separation. (Alberti S, 2017)

Customized Services

Biomolecular condensates strongly depend on the concentration of the biomolecule of interest. We offer in vitro liquid-liquid phase separation experiments to precisely measure light or dense phase concentrations of C_L and C_D. Here, CD BioSciences focuses on how cells manipulate biomolecule concentrations to construct and maintain biomolecular condensates with defined properties. We offer the following strategies:

• Alteration of protein concentrations
  We can analyze protein concentration changes to regulate whether biomolecular condensates are formed. Our experts directly analyze this by altering transcription, translation and protein degradation to change overall protein concentration, or by restricting the protein of interest at specific cellular focal points and regulating protein binding to membranes to change protein concentration locally.
• Alteration of RNA concentrations
  RNA concentration has a regulatory effect on the occurrence of abnormal phase separation. We focused on the effect of altered RNA concentration on the aberrant phase separation behavior of fusion sarcoma (FUS, a typical RNA-binding protein) in the cytoplasm. We aim to find the cause of abnormal phase separation in the FUS cytoplasm to develop effective therapies.

We develop customized experiments to analyze the regulation of biomolecular phase separation by concentration changes, including:

• The effect of concentration changes on the timing and location of condensates aggregation.
• The effect of concentration changes on the rate of condensates assembly and disassembly.
• The effect of concentration changes on the material and biophysical properties of condensates.

Living cells regulate the assembly of biomolecular condensates by changing the concentration of biomolecules. Our services aim to provide an understanding of phase separation to develop new therapeutic strategies for LLPS-related diseases. If you have any special requirements for our services, please feel free to contact us. We are looking forward to working together with your attractive projects.