Self-organization of biomolecules can lead to the formation of liquid droplets, hydrogels, and irreversible aggregates that bear immense significance in biology and diseases. Despite the considerable number of studies conducted on biomolecular condensation in bulk solution, there is still a lack of understanding of how different surfaces regulate the condensation process. In this context, recent studies showed that, in contrast to zwitterionic lipid membranes, anionic membranes promoted the production of liquid droplets of FUsed in Sarcoma Low Complexity domain (FUS-LC) despite exhibiting no specific protein-lipid interactions. Moreover, the air–water interface led to a solid fibril-like aggregate of FUS-LC. The molecular mechanism of condensation/aggregation of proteins in response to surfaces of various charged states or levels of hydrophobicity remains to be better elucidated. Here, we provide initial insights into this question by investigating the stability of a small β fibril state of FUS-LC in bulk solution vs. membrane- and air–water interfaces. We perform multiple independent molecular dynamics simulations with distinct starting conformations for each system to demonstrate the statistical significance of our findings. Our study demonstrates the stability of the FUS-LC fibril in the presence of anionic membranes on the μs timescale while the fibril falls apart in bulk solution. We observe that a zwitterionic membrane does not enhance the stability of the fibril and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) has a higher propensity to stabilize the fibril than dioleoylphosphatidylglycerol (DOPG), in qualitative agreement with experiments. We further show that the fibril becomes more stable at the air–water interface. We pinpoint interfacial solvation at the membrane- and air–water interfaces as a key factor that contributes to the stabilization of the peptide assembly.
This article is Open Access
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