When a membrane meets a droplet

Cells are the building blocks of our bodies. To perform the different functions required for life, cells organize their components (i.e. water, ions, lipids, proteins, DNA) in compartments called organelles. These organelles perform specialized functions, just like the different organs do in our body. While for a long time scientists have thought that all organelles were surrounded by a membrane (membrane-bound organelles), now we know that some components can condense into droplets as membrane-less organelles with liquid-like properties. These membrane-less organelles are known as biomolecular condensates. Little is known yet about the interaction between these biomolecular condensate droplets and the membrane-bound organelles. Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam developed synthetic membraneless organelles and visualized what happens when they meet a membrane. They showed that the interaction of biomolecular condensates and membranes can mutually reshape them and lead to dramatic morphologic changes, which can be tuned by changing external condition.

Cells are the fundamental units of life, providing a unique and dynamic environment that enables the organization of molecules and chemical reactions necessary to sustain life. Within each cell, there are countless molecules, such as DNA, proteins, sugars, and lipids, that interact with each other in different ways. Scientists have been working to understand how cells organize these components to function in complex environments by creating synthetic cells with fewer components. This emerging field, known as synthetic biology, combines principles of engineering and biology to simplify and recreate natural biological systems. By taking apart and reconstructing natural components, researchers hope to engineer simple systems that can mimic certain cellular processes, enabling breakthroughs in medicine, biotechnology, and other areas.

The cells and compartments inside them (organelles) are typically bound by a membrane. However, cells also have membrane-less organelles, called biomolecular condensates, that do not have a physical barrier around them, but they are made up of a mixture of different molecules that can stick together. These biomolecular condensates are found inside cells and help to keep things organized by separating different types of molecules into different areas. For example, some membrane-less organelles might contain a lot of proteins. By separating the proteins from other molecules in the cell, these organelles can protect them from degradation and regulate the activity of proteins by bringing them into close proximity thus facilitating interactions between them. They can also help to control the timing and location of protein activity within the cell. Scientists are studying membraneless organelles to learn more about how cells work and how they might be involved in cell physiology and also in diseases.

What happens when biomolecular condensates interact with membrane-bound organelles? This is a legitimate question, considering the abundance of membranous intracellular structures which makes the encounter with the droplets inevitable. The research team headed by Rumiana Dimova at the Max Planck Institute of Colloids and Interfaces explored this issue by using lipid membranes and biomolecular condensates as synthetic membrane-less organelles. By means of fluorescence microscopy, they showed that upon contact, biomolecular condensates can stick to membranes and spread, just like a droplet can sit or spread on a surface. However, because the membranes are a soft substrate, the biomolecular condensates can also deform and shape membranes, while simultaneously deforming themselves. Dr. Agustin Mangiarotti from the Dimova group observed that whether droplets like to spread on membranes or not can be tuned by simple parameters such as the salinity of the environment or by changing the membrane properties and composition. These results suggest that cells could take advantage of these interactions to modulate their organelle shape and interactions. The team described a new phenomenon, namely “interfacial ruffling” which is a mutual remodeling process that produces complex curved protrusions (see Image). The protrusions resemble the morphology of intracellular structures, such as the tubular network connecting the Golgi apparatus with the endoplasmic reticulum.

This work constitutes a step forward towards understanding the interaction between biomolecular condensates and membrane-bound organelles in cells, showing that biomolecular condensates can act as sculptors of intricate membrane structures, generating local curvature without the involvement of active processes. Additionally, these observations could pave the road to designing synthetic membrane-droplet based biomaterials and compartments with tunable properties.