Biophysical Services for Liquid-Liquid Phase Separation
Liquid-liquid phase separation (LLPS) is an emerging phenomenon that involves various biological processes such as signaling, RNA metabolism, and stress adaptation, etc. As an ideal partner for biomolecular condensates, CD BioSciences provides customized biophysics services of liquid-liquid phase separation for customers worldwide to explore the detailed biophysical processes involved in the formation of membrane-free organelles from LLPS in cells.
Introduction to The Driving Forces of LLPS
LLPS typically occurs between two immiscible liquids, such as water and octanol. LLPS is caused by repulsive forces between different polymers, and the solvent plays a role in diluting these repulsive contacts. In recent years, LLPS has attracted a lot of attention in biological systems (cytoplasm and nucleoplasm), because membraneless organelles including nucleoli, Cajal bodies, centrosomes, membrane receptor clusters, P-bodies and stress granules are formed by LLPS caused by protein and nucleic acid interactions. LLPS is an important and widespread phenomenon for the formation of biomolecular condensates in eukaryotic cells. These structures play different roles in various biological processes and are also increasingly associated with protein aggregation diseases. The driving forces of LLPS are usually based on weak, transient and multivalent interactions, including interactions between proteins with multiple repetitive structural domains and a long string of intrinsically disordered regions (IDRs). The various molecular forces that drive phase separation are not fully understood.
Fig. 1. LLPS phase separation in vitro and in vivo. (Gomes E, et al, 2019)
Customized Services
Biomolecular condensates are largely physically supported by LLPS, but the detailed biophysical processes within cells that lead to these assemblies remain largely unexplored. With water at the center of our research, our team of experts is committed to the theoretical study of the role of LLPS in the assembly and dissociation of membraneless organelles, including:
- Analysis of the Nature and Interfacial Tension of Water in Coexisting Phases
We provide liquid characterization and interfacial tension analysis of a range of condensates in polymers by analyzing the properties of water in solutions of macromolecules, small organic compounds, electrolytes and their mixtures.
- Generation of Phase Diagrams for Aqueous Two-Phase Systems
We generate phase diagrams to characterize aqueous two-phase systems by showing the composition of two co-existing phases of a mixture of two polymers in water with various overall compositions by the following method.
- Phase separation treatment based on the Flory-Huggins theory.
- Theoretical treatment based on the Viry expansion model.
- Theoretical treatment based on the exclusion volume principle.
LLPS usually involves intrinsically disordered proteins involved in multivalent interactions controlled by their amino acid sequences. In close collaboration with biophysicists, CD BioSciences provides bioinformatics tools, computational methods and in vitro experiments to analyze the molecular driving forces of LLPS. The numerical procedures covered include:
- Procedures for determining spin-node line and double-node line phase boundaries from general free energy functions.
- Examples based on random phase approximations in polymer theory.
- Linkage line construction of multicomponent LLPS.
- Field theory simulations of multicomponent - chain heteropolymer systems.
In addition, since a more accurate physical picture usually requires comparing analytical theory with explicit chain model predictions, we use theoretical formulations of atomic and coarse-grained representations and molecular dynamics simulations to characterize the phase behavior and microstructural features of polymers in dense condensed layers. Our biophysical services for LLPS include but are not limited to:
With years of experience in biomolecular condensates, CD BioSciences offers professional and cost-effective biophysics services program for LLPS. We help you analyze how molecular interactions affect the stability, structure, and kinetics of liquid-liquid phase separations in protein condensates. Each project will be individually designed to meet the client's requirements and described in a detailed project report. If you are interested in our services, please contact us.
