Abstract:Liquid–liquid phase separation is a fundamental biophysical process to organize eukaryotic and prokaryotic cytosols. While many biomolecular condensates are formed in the vicinity of, or even on lipid membranes, little is known about the interaction of protein condensates and lipid bilayers. In this study, we characterize the recently unknown phase behavior of the bacterial nucleoid occlusion protein Noc. We find that, similarly to other ParB-like proteins, CTP binding tightly regulates Noc’s propensity to pha… Show more
“…26 . Additionaly, it has been reported that membranes can regulate the assembly and nucleation of condensates 14, 15 . However, to the best of our knowledge, there are no studies aiming to elucidate the mechanism behind the membrane-condensate interaction.…”
Section: Discussionmentioning
confidence: 99%
“…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.…”
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.
“…26 . Additionaly, it has been reported that membranes can regulate the assembly and nucleation of condensates 14, 15 . However, to the best of our knowledge, there are no studies aiming to elucidate the mechanism behind the membrane-condensate interaction.…”
Section: Discussionmentioning
confidence: 99%
“…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.…”
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.
“…It is straightforward to verify that the latter volume fraction is proportional to the assembly threshold defined in (11), i.e. φ = e/(1 − e) 2 ϕ * .…”
Section: Discussionmentioning
confidence: 99%
“…The biological function of both assemblies and phaseseparated compartments relies on the recruitment of specific biomolecules such as proteins, RNA or DNA [4][5][6][7]. Since assemblies and condensed phases can adhere to membrane surfaces, both not only mediate mechanisms for sorting and transport of molecules [8] but also affect the composition, shape and properties of intra-cellular surfaces [9][10][11][12]. Despite these similarities, molecular assemblies and coexisting phases also exhibit crucial differences.…”
Interactions among proteins in living cells can lead to molecular assemblies of different sizes and large-scale coexisting phases formed via phase separation. Both are essential for the spatial organization of cells and for regulating biological function and dysfunction. A key challenge is understanding the interplay between molecular assembly and phase separation. However, a corresponding theoretical framework that relies on thermodynamic principles is lacking. Here, we present a non-equilibrium thermodynamic theory for a multi-component mixture that contains assemblies of different sizes, which can form, dissolve, and phase-separate from the solvent. We show that the size distributions of assemblies differ between the phases and that the dense phase can gelate. Moreover, we unravel the mechanisms involved in growth and compositional changes of the coexisting phases during assembly kinetics. Our theory can explain how molecular assembly is intertwined with phase separation, and our results are consistent with recent experimental observations on protein phase separation.
“…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.…”
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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