To stick or not to stick:
a new understanding of condensates-membranes interactions
TAKEAWAYS:
- Challenge: It's not just whether a membrane is in a "solid" or "liquid" state that matters—how tightly its molecules are packed also influences how protein-rich droplets (condensates) stick to it
- Finding: More tightly packed membranes push away condensates, while loosely packed ones attract them
- Impact: Understanding these interactions is key to grasping essential cellular functions. Disruptions in condensate-membrane interactions could affect cellular communication, protein synthesis, and disease progression
Biomolecular condensates are tiny droplets inside cells composed of proteins and other molecules—but unlike all other organelles, they lack the surrounding membrane.
Rumiana Dimova and her team are fascinated by how these membraneless droplets interact with their membrane-bound neighbors. When condensates stick to membranes, they reshape them into disk-like and tubular forms.
“Within cells, every interaction serves a specific function. Think of membranes as specialized labs: they create compartments where biochemical reactions can unfold smoothly, and regulate the passage of substances. Condensates offer further compartmentalization by sticking to the membranes in different ways—or not at all. Their behavior is similar to that of water drops, which can spread or bead up depending on the surface they interact with. This is what we technically call wetting”. explains Dr. Agustín Mangiarotti.
After serving as temporary compartments, biocondensates can dissolve, leaving behind a series of questions for scientists to solve.
In their latest study, Dimova and team challenged the accepted scholarly view that a membrane’s phase is the decisive factor determining condensates’ wetting.
“We shouldn't think of membranes as rigid walls. On the contrary, they are bilayers of fat molecules arranged in long or short chains. They can thus exist in different phases—liquid or solid-like. A well-known fat, cholesterol, plays a crucial role in modulating how rigid or fluid membranes are. The more liquid they are, the more they stick to condensate droplets.”—adds Dimova.
By combining advanced microscopic imaging, precise biophysical measurements, and synthetic cell models, the researchers demonstrated that how tightly the fatty molecules are packed—not just membrane phase—controls how condensates interact with membranes.
The denser the lipid packing in a membrane, the less likely condensates are to stick to it, largely due to the reduced hydration of tightly packed membranes. Conversely, loosely packed membranes tend to attract condensates, as they provide a "wetter" surface.
Understanding these mechanisms means understanding the complex environment inside cells—or how life operates at a fundamental level. It also provides insight into what happens when these processes go wrong, leading to issues in cellular communication, protein synthesis, and disease.
Explore related projects at the ComeInCell Doctoral Network
