Condensate-mediated shape transformations of cellular membranes by capillary forces

Phase-separated biomolecular condensates with liquid-like properties play a key role in the organization and compartmentalization of the intracellular environment. Condensate-mediated capillary forces acting on membranes drive physiologically important reshaping of membrane-bound organelles, such as vacuoles and autophagosomes. Here, we explore condensate-mediated membrane shape transformations. We employ {\textit{in planta}} live-cell imaging, an \textit{in vitro} reconstitution system with tunable interfacial tension, and computer simulations of an elastic membrane model to describe three morphologies of membrane structures localized at condensate interfaces: tubes, sheets, and cups. We find that the forces associated with high interfacial tension drive the formation of stable sheets, while tubes and cups prevail at lower interfacial tension. We calculate the free energies of each membrane shape and identify the energy barriers that govern the transitions between the shapes. With this approach, we find that shape transformations depend on the history of the interfacial membrane and exhibit a tube-to-cup hysteresis. These findings indicate that temporal control of condensate surface properties can mediate the morphogenesis of cup-like structures in cells, such as the formation of “bulbs” within plant vacuoles. Our results further generalize how the interplay of condensates and membranes contributes to intracellular organization.

💡 Research Summary

This study investigates how liquid‑like biomolecular condensates generate capillary forces that remodel cellular membranes into tubes, sheets, and cup‑shaped structures. The authors combine three complementary approaches: (i) live‑cell imaging of Arabidopsis thaliana embryos, (ii) an in‑vitro reconstitution system using giant unilamellar vesicles (GUVs) that encapsulate a phase‑separating polymer mixture, and (iii) coarse‑grained computer simulations of an elastic membrane coupled to interfacial tension.

In planta, the authors observe that storage‑protein condensates forming during seed maturation partially wet the tonoplast (vacuolar membrane). At the liquid‑liquid interface, flattened “sheets” and closed “cups” appear as double‑membrane structures that fluoresce roughly twice as strongly as the surrounding tonoplast, indicating two closely apposed bilayers separated by sub‑200 nm gaps. These structures correspond to the previously described “bulbs” in plant vacuoles.

In the reconstituted system, hyper‑osmotic quenching creates a PEG‑rich and a dextran‑rich phase inside GUVs, establishing a well‑defined liquid‑liquid interface. Initially, tubular membrane protrusions decorate the interface, mirroring early‑stage condensate‑tonoplast contacts. Over hours to days, the tubes give way to planar sheets and spherical cups. Stimulated emission depletion (STED) microscopy resolves the membrane spacing: sheets have bilayers ~204 nm apart, cups ~105 nm. The spacing falls within the range where electrostatic repulsion (modeled by DLVO theory) dominates, suggesting that charge‑mediated forces stabilize the double‑membrane architecture without direct contact.

Time‑lapse imaging shows that tubes can remain metastable for >24 h before a rapid (<1 min) transition to multiple sheets, which then coalesce slowly. The coexistence of distinct morphologies and the delayed transitions imply a rugged energy landscape with significant barriers.

To rationalize these observations, the authors employ an elastic membrane model that incorporates bending rigidity, surface tension, and a capillary term proportional to the interfacial tension Σ. Free‑energy calculations reveal that high Σ favors sheet formation (global energy minimum), whereas low Σ makes tubes and cups metastable minima separated by barriers. The tube‑to‑cup transition exhibits hysteresis: the system must overcome a higher barrier when moving from tube to cup than in the reverse direction, making the pathway history‑dependent.

Key insights include: (1) interfacial tension is a primary control knob for membrane morphology; (2) electrostatic repulsion between closely apposed bilayers determines the equilibrium spacing of sheets and cups; (3) shape transitions are governed by non‑equilibrium kinetics and energy barriers, not merely by thermodynamic minimization. The work thus provides a mechanistic explanation for the formation of plant vacuolar “bulbs” and suggests that temporal regulation of condensate surface properties can drive morphogenesis of cup‑like organelles.

Overall, the paper bridges cell biology, soft‑matter physics, and computational modeling to elucidate how condensate‑membrane wetting and capillary forces orchestrate membrane remodeling, offering a general framework applicable to diverse cellular contexts and to the design of synthetic organelle systems.