[Paper Review] Condensate-mediated shape transformations of cellular membranes by capillary forces

Lukas Hauer, Katharina Sporbeck+6 more|arXiv (Cornell University)|Mar 16, 2026

Lipid Membrane Structure and Behavior0 citations

TL;DR

The paper demonstrates that phase-separated biomolecular condensates induce capillary forces at condensate-membrane interfaces, driving metastable membrane shapes (tubes, sheets, cups) and hysteresis governed by interfacial tension; it combines in vivo plant vacuole observations, in vitro reconstitutions with tunable interfacial tension, and in silico membrane models to map energy landscapes and transition dynamics.

ABSTRACT

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 { extit{in planta}} live-cell imaging, an extit{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.

Motivation & Objective

• Understand how condensate wetting reshapes membranes at liquid–liquid interfaces in cells.
• Quantify how interfacial tension controls membrane morphologies (tubes, sheets, cups).
• Characterize energy barriers and metastability governing shape transitions.
• Disentangle equilibrium vs. non-equilibrium (hysteresis) effects on interfacial membranes.
• Translate findings to potential cellular morphogenesis, e.g., plant vacuole bulbs.

Proposed method

• In planta live-cell imaging of Arabidopsis thaliana cotyledons to observe interfacial sheets and cups at vacuole interfaces.
• In vitro reconstitution using phase-separated polymer solutions within giant Unilamellar Vesicles (GUVs) to tune interfacial tension Sigma.
• Coarse-grained Monte Carlo (MC) minimization and MC simulations of triangulated vesicles to compute free-energy landscapes with parameters v (volume-to-area ratio) and sigma (reduced interfacial tension).
• Analytic tests of variable contact angle theta to assess robustness of energy predictions.
• STED microscopy to resolve membrane spacing and confirm bilayer separation.
• Analytical and numerical comparison of in vitro/free-energy differences with in silico results.

Figure 1: Condensates within plant vacuoles shape internal membrane structures. (A) Each individual A. thaliana plant can be used to sample multiple developmental stages of their embryos. Each fruit (seed capsule) contains 30-60 seeds (light gray) with a single embryo. (B) Embryo cells (white dashed

Experimental results

Research questions

• RQ1 How do condensate–membrane interfacial capillary forces shape membranes into tubes, sheets, and cups?
• RQ2 How does interfacial tension Sigma influence the stability and transitions among interfacial morphologies?
• RQ3 What are the energy barriers between tubular, sheet, and cup morphologies, and how do they depend on volume-to-area ratio v and interfacial tension sigma?
• RQ4 Is there hysteresis in shape transformations due to non-equilibrium metastability, and what controls it?
• RQ5 How well do in silico models reproduce in vitro observations and what factors explain discrepancies?

Key findings

• Interfacial membranes at condensate interfaces form three morphologies: tubes, sheets, and cups, observable in vivo and in vitro.
• Higher interfacial tension Sigma stabilizes sheets and reduces energy barriers, promoting tube-to-sheet transitions; lower Sigma favors cups.
• Energy barriers H1 (tube→sheet) and H2 (sheet→cup) are modulated by sigma and v, predicting a morphological diagram with regions for tubes, sheets, and cups.
• Shape transitions exhibit hysteresis; tube-to-sheet and sheet-to-cup transitions depend on history and are activated by thermal fluctuations.
• MC simulations and experiments show that tubes are more prone to initial formation, but sheets precede cups; cups more likely at low Sigma, sheets at high Sigma.
• Free-energy comparisons indicate cups have lower energy at low Sigma, while sheets become energetically favorable at high Sigma; discrepancies between in vitro and in silico tube energies are discussed.

Figure 2: Membrane structures at liquid-liquid interfaces inside GUV. (A) Left, schematics of GUVs (green) cut in half for illustration purposes. The GUV interior is filled with homogeneous dextran/PEG solutions (light magenta). It undergoes phase separation upon hyperosmotic quenching, forming an u