Biomolecular condensates modulate membrane lipid packing and hydration

Abstract

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.

Coacervate Droplets for Synthetic Cells

“…In addition, similar to condensates in living cells, [186] coacervate droplets wet lipid bilayers, as very recently evidenced in vitro upon mixing different types of coacervates, including complex DNA nanostars and biological coacervates, with giant unilamellar vesicles (GUVs) [196,[204][205][206][207][208][209] (Figure 5n,o). This wetting behavior has been shown to perturb the organization of lipids within bilayers, either producing pores [195] or increasing lipid packing.…”

“…This wetting behavior has been shown to perturb the organization of lipids within bilayers, either producing pores [195] or increasing lipid packing. [205] Remarkably, capillary forces on soft and deformable lipid bilayers generate elastocapillary effects that have been reported to result in significant membrane deformations, such as fingering [206] and nanotube formation. [207][208][209] In a striking example, complete engulfment of coacervate droplets adsorbed on the external surface of GUVs has been observed, driven by charge interactions with lipids, ultimately leading to the formation of lipid-coated coacervates within vesicles in a process reminiscent to endocytosis [204] (Figure 5n).…”

“…Possible outcomes of such programmable coacervate-membrane interactions could be the local recruitment of proteins at the membrane, the remodeling of membranes, e.g., to achieve internally triggered endocytosis, or the alteration of the membrane permeability (e.g., via a change in lipid packing [205] ), which could ultimately regulate signal transduction across membranes.…”

Interfacing Coacervates with Membranes: From Artificial Organelles and Hybrid Protocells to Intracellular Delivery

“…Dimova and co–workers also found that glycinin protein condensates enhanced the packing of DOPC lipids and reduced membrane fluidity, in agreement with the observed wetting of glycinin condensates on GUVs. [ 47 ] These findings suggest that coacervate interactions with phospholipid head groups, which are required for membrane templating, correlate with enhanced lipid packing and reduced fluidity, which could provide a way to tune membrane properties, for example, by the addition of salt. The enhanced permeability of coacervate‐templated membranes is therefore likely caused by the presence of (transient) membrane defects.…”

Synthetic syntrophy: A platform technology for adenine nucleotide cross-feeding between metabolically active vesicles

“…Additionally, biomolecular condensates can be important for the efficiency of reactions or tuning of membrane properties. 3,4 The mimicry of a living cell, which can autonomously replicate and sustain itself, has advanced the engineering of metabolic systems. [5][6][7][8] The regeneration of ATP as a versatile metabolic energy carrier for biosynthesis has been the focus, [9][10][11][12][13][14][15][16][17] but homeostasis of pH and volume, and control of nonspecific interactions between components are also essential for a cell.…”