# Insights into de-mixing and morphology modulation in coacervate-membrane interactions from integrating experiments and simulations

## TL;DR

This study explores how coacervates interact with membranes, revealing how lipid content affects membrane behavior and structure.

## Contribution

The integration of experiments and simulations provides a novel framework for understanding coacervate-membrane interactions.

## Key findings

- Membrane fluidity is nearly two-fold reduced where it contacts the coacervate due to lipid crowding.
- Local lipid de-mixing occurs upon coacervate adsorption, indicating structural changes at the interface.
- Membrane affinity of coacervates is tunable by anionic lipid content and quantifiable via contact angle.

## Abstract

Intrinsically disordered proteins can undergo liquid-liquid phase separation to form condensates or coacervates, which play numerous regulatory roles in the cell. Recently, it was recognized that membrane-adsorbed condensates are crucial for biomolecular localization, and in some cases, induce significant changes in membrane morphology. A detailed understanding of the underlying mechanisms remains incomplete. Here, we combine experiments and simulations to unravel structural and dynamic features of the coacervate/membrane interface across scales. We study poly-Lysine/poly-Aspartate (K10/D10) coacervates with different unilamellar liposomes. By combining confocal microscopy, hyperspectral imaging, fluorescence recovery after photobleaching, and two complementary coarse-grained approaches, we show that the membrane affinity of the K10/D10 coacervate can be tuned by the anionic lipid content and quantified through the intrinsic contact angle, both in vitro and in silico. We find that the membrane in contact with the condensate displays a nearly two-fold reduced fluidity compared to the bare membrane. This is attributed to the crowding of lipids at the contact region, resulting in decreased area per lipid. Moreover, we observed local lipid de-mixing upon coacervate adsorption. This study provides an effective framework for integrating experiment and computation to characterize the properties of coacervate-membrane interfaces that are critical to the functional impacts of these interactions.

Membrane-adsorbed condensates are crucial for biomolecular localization and can induce significant changes in membrane morphology, but the underlying mechanisms remain underexplored. Here, the authors combine imaging experiments and coarse-grained simulations to study poly-Lysine/poly-Aspartate (K10/D10) coacervates with different unilamellar liposomes, showing that their membrane affinity can be tuned by the anionic lipid content and quantified through the intrinsic contact angle both in vitro and in silico.