Coupling of protein condensates to ordered lipid domains determines functional membrane organization

Wang, Hongyin; Chan, Sze Ham; Dey, Santanu S.; Castello-Serrano, Ivan; Ditlev, Jonathon A.; Rosen, Michael K.; Levental, Kandice R.; Levental, Ilya

doi:10.1101/2022.08.02.502487

Cited by 23 publications

(23 citation statements)

References 65 publications

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“…Importantly, each of these assemblies involves protein-protein interactions on both surfaces of the membrane. In such processes, we speculate that the entropic coupling mechanism identified here works in concert with transmembrane proteins and lipid phase separation 38 to achieve robust transbilayer coupling and communication.…”

Section: Discussionmentioning

confidence: 90%

Lateral compression of lipids drives transbilayer coupling of liquid-like protein condensates

Lee

Park

Feng

et al. 2022

Preprint

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Liquid-liquid phase separation of proteins has recently been observed on the surfaces of biological membranes, where it plays a role in diverse cellular processes, from assembly of focal adhesions and the immunological synapse, to biogenesis of trafficking vesicles. Interestingly in each of these cases, proteins on both surfaces of the membrane are thought to participate, suggesting that protein phase separation could be coupled across the membrane. To explore this possibility, we used an array of freestanding planar lipid membranes to observe protein phase separation simultaneously on both surfaces of lipid bilayers. When proteins known to engage in phase separation bound to the surfaces of these membranes, two-dimensional, protein-rich phases rapidly emerged. These phases displayed the hallmarks of a liquid, coarsening over time by fusing and re-rounding. Interestingly, we observed that protein-rich domains on one side of the membrane colocalized with those on the other side, resulting in transbilayer coupling. How do liquid-like protein phases communicate across the lipid bilayer? Our results, based on lipid probe partitioning and the differential mobility of proteins and lipids, collectively suggest an entropic coupling mechanism, which relies on the ability of protein phase separation to locally reduce the entropy of the underlying lipid membrane, most likely by increasing lipid packing. Regions of reduced entropy then colocalize across the bilayer to minimize the overall free energy of the membrane. These findings suggest a previously unknown mechanism by which cellular signals originating from one side of the membrane, triggered by protein phase separation, can be transferred to the opposite side.

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Section: Discussionmentioning

confidence: 90%

Lateral compression of lipids drives transbilayer coupling of liquid-like protein condensates

Lee

Park

Feng

et al. 2022

Preprint

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“…Recently, membranes have been reported to control the size of intracellular condensates and modify their material properties 14 . Furthermore, the crosstalk between membranes and condensates can promote phase separation coupling in the lipid and the protein phases 15,16,17 also shown in cytoplasm mimicking systems 18 . In this manner, membrane-condensate interactions have become an emerging and exciting field, but important cues are still missing towards understanding the underlying mechanisms of the resulting structural changes and remodeling.…”

Section: Introductionmentioning

confidence: 99%

Biomolecular condensates modulate membrane lipid packing and hydration

Mangiarotti

Siri

Zhao

et al. 2023

Preprint

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Membrane wetting by biomolecular condensates recently emerged as a critical phenomenon in cell biology, involved in a great diversity of processes across different organisms. However, understanding the molecular mechanism behind this process is still missing. Exploiting ACDAN and LAURDAN properties as nano-environmental sensors in combination with phasor analysis of hyperspectral and lifetime imaging microscopy, we obtained vital information on the process of condensate formation and membrane wetting. The results reveal that glycinin condensates display differences in water dynamics when changing the salinity of the medium as a consequence of rearrangements in the secondary structure of the protein. The analysis of membrane-condensates interaction indicated a correlation between increased wetting affinity and enhanced lipid packing, demonstrated by a decrease in water dipolar relaxation at both protein and polymer systems. These results suggest a general mechanism to tune membrane order by condensate wetting.

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“…While several studies have already addressed the effect of membrane composition and phase state on the interaction with condensates 27,28 , as well as the coupling between lipid domains and condensates 29,30 , we focused on understanding the mechanism of membrane wetting and remodeling by condensates. Here, we provide a systematic analysis of the membrane remodeling and wetting behavior of GUVs exposed to water-soluble proteins that phase separate into a protein-rich and a protein-poor phase.…”

Section: Introductionmentioning

confidence: 99%

Wetting and complex remodeling of membranes by biomolecular condensates

Mangiarotti

Chen

Zhao

et al. 2022

Preprint

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Cells compartmentalize their components in liquid-like condensates, which can be reconstituted in vitro. Although these condensates interact with membrane-bound organelles, the potential of membrane remodeling and the underlying mechanisms are not well understood. Here, we demonstrate that interactions between protein condensates and membranes can lead to remarkable morphological transformations and describe these with theoretical analysis. Modulation of solution salinity or membrane composition drives the condensate-membrane system through two wetting transitions, from dewetting, through a broad regime of partial wetting, to complete wetting. The observed morphologies are governed by the interplay of adhesion, membrane elasticity and interfacial tension. A new phenomenon, namely reticulation or fingering of the condensate-membrane interface is observed when sufficient membrane area is available, producing complex curved structures. Our results highlight the relevance of wetting in cell biology, and pave the way for the design of synthetic membrane-droplet based biomaterials and compartments with tunable properties.

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Coupling of protein condensates to ordered lipid domains determines functional membrane organization

Cited by 23 publications

References 65 publications

Lateral compression of lipids drives transbilayer coupling of liquid-like protein condensates

Lateral compression of lipids drives transbilayer coupling of liquid-like protein condensates

Biomolecular condensates modulate membrane lipid packing and hydration

Wetting and complex remodeling of membranes by biomolecular condensates

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