Analysis of Control Centers of Biomolecular Condensate Phase Separation

Biomolecular condensates are membrane-free structures formed by liquid-liquid phase separation (LLPS) driven formation. Phase-separated structures can be found throughout the physiological environment of the cell and display unique functional and biophysical characteristics. Biomolecular condensation relies on weak multivalent interactions between proteins and nucleic acids. So how does the cell control these interactions to regulate phase separation? Cells typically manipulate a number of key parameters including the concentration of molecular components, the chemical valence and strength of intermolecular interactions, initial nucleation or crystal species events, environmental parameters, and thermodynamic parameters to construct and maintain biomolecular condensates with defined properties and characteristics. In addition, cells can control the timing and location of condensate aggregation, the rate of assembly and disassembly, and the material and biophysical properties of condensates.

Fig. 1. Regulation and misregulation of biomolecular condensation. (Garcia-Cabau C, et al., 2021)

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Different cellular processes depend on biomolecular condensates and help regulate transcription, translation and protein degradation, while abnormal phase separation can lead to disease. In turn, cells can temporally and spatially regulate the material properties of biomolecular condensates by regulating phase separation on a faster time scale. Such regulation can be achieved by different means, including alteration of protein concentration, stabilization of the condensates's interaction strength, post-translational modifications (PTM), or by active energy-consuming processes that solubilize the condensates and/or control its material properties. Our team of experts has developed extensive expertise in this area, and is dedicated to studying the mechanisms by which cells control these interactions to regulate phase separation.

CD BioSciences offers specialized services to analyze the control centers for biomolecular condensate phase separation. The key cellular mechanisms we focus on are included but not limited to as follows:

• Membrane Surfaces
  Membrane surfaces are important regulatory platforms for the controlled assembly of biomolecular condensates. Specifically, membrane surfaces confine molecular diffusion to a two-dimensional plane, lower the concentration threshold for phase separation, and control the timing and location of nucleation. Starting with the endomembranes, endocytosis and lipid aspects, our service aims to analyze how membranes control the assembly of condensates throughout the cell, and to examine the specific mechanisms by which proteins and nucleic acids are recruited to the endosomal surface prior to phase separation.
• Activation Processes
  Once phase separation has occurred, cells must maintain and remodel biomolecular condensates to meet specific cellular demands. We focus on how cells actively modify condensates to meet different demands, by analyzing the active regulation of biomolecular condensates by molecular chaperones and RNA uncoupling enzymes.
• Post-Translational Modifications
  PTM can modulate protein valence and interaction strength to promote or oppose phase separation under different circumstances, thereby tuning the properties and overall function of condensates. We provide key examples of the analysis of PTMs that regulate phase separation and the measurement of phase separation of RNA-binding proteins during PTM.
• 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. We offer professional services to analyze the regulation of biomolecular phase separation by concentration changes.
  

Cells must control the natural tendency of protein and nucleic acid phase separation in order to construct functional condensates at the correct time and location. However, the mechanisms by which cells control this process to produce functional phase separation structures are only just beginning to be discovered. Our service aims to elucidate how these diverse and complex regulatory systems coordinate to ensure robust phase separation. 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.