Understanding Liquid–Liquid Phase Separation
A New Frontier in Cell Biology
Liquid–liquid phase separation (LLPS) is rapidly gaining recognition as a foundational mechanism in cell biology, biophysics, and therapeutic innovation. Once considered cellular noise, LLPS is now known to organise biomolecules into dynamic, membrane-less compartments known as biomolecular condensates. These liquid-like structures play critical roles in gene regulation, RNA metabolism, and signal transduction, offering a powerful new lens through which to understand health and disease.
Dynamic comparison between generic membrane-bound organelle (left) and biocondensate (right)
What Is Liquid–Liquid Phase Separation?
LLPS refers to the spontaneous segregation of molecules, typically proteins and nucleic acids, into two distinct liquid phases within a cell. This process is akin to how oil separates from water. In biology, LLPS allows cells to form compartmentalised structures without the need for lipid membranes. These membrane-less organelles, including stress granules, nucleoli, and P-bodies, can form quickly in response to stimuli and dissolve just as rapidly, enabling agile cellular responses.
At the molecular level, LLPS is driven by multivalent interactions among proteins and RNAs. Disordered regions in proteins, often rich in repetitive sequences, promote these interactions and facilitate the formation of dynamic condensates. These structures concentrate biochemical reactions, buffer noise in signaling pathways, and serve as hubs for tightly regulated cellular processes.
LLPS in Health and Disease
Understanding LLPS has transformed how scientists approach diseases ranging from neurodegeneration to cancer. For example, abnormal phase separation has been implicated in ALS, Alzheimer’s disease, and Huntington’s disease, where defective protein-RNA interactions lead to pathological aggregates. Conversely, harnessing LLPS is now a strategy to design synthetic organelles or reprogram cellular environments for therapeutic benefit.
In cancer biology, LLPS influences the spatial and temporal control of transcription factors and epigenetic modifiers. In viral infections, it affects how host cells sequester viral components. The wide relevance of LLPS has positioned it at the cutting edge of drug discovery, synthetic biology, and intracellular delivery technologies.
LLPS in Biotechnology: From Discovery to Delivery
Biotechnologists are increasingly leveraging LLPS to engineer intracellular delivery platforms, biosensors, and drug screening tools. Because LLPS enables the dynamic packaging and release of biomolecules, it is particularly well-suited for delivering RNA, DNA, and proteins in a controlled, responsive way.
This has profound implications for the future of biologics. Traditional delivery systems, such as lipid nanoparticles or viral vectors, can be limited by toxicity, scalability, or cold-chain requirements. LLPS-inspired systems, on the other hand, offer self-assembling, temperature-stable, and low-toxicity alternatives that are easier to manufacture and more adaptable to diverse cell types and applications.
Introducing BubbleFect: LLPS-Driven Delivery for the Next Generation of Therapeutics
Built on LLPS science, BubbleFect is PartitionBio’s breakthrough delivery platform that brings the power of biomolecular condensates into everyday lab workflows. Designed as a non-viral, room-temperature stable reagent, BubbleFect enables the gentle and efficient delivery of nucleic acids and proteins into a broad range of cell types, with minimal toxicity and high reproducibility.
Unlike conventional methods that rely on harsh chemicals, electrical pulses, or lipid-based formulations, BubbleFect uses LLPS-inspired self-assembly to create delivery-ready formulations in minutes. Users simply mix their cargo in water, add the reagent, and apply it to cells, no special equipment or cold storage required.
Whether you're delivering mRNA, CRISPR components, or proteins, BubbleFect brings the advantages of LLPS into the hands of researchers, helping accelerate discovery and unlock new therapeutic possibilities.