Lipid Composition Modulates Secondary Structure at the Biocondensate-Membrane Interface

Abstract

Biomolecular condensates (BMCs) formed through liquid-liquid phase separation (LLPS) play key roles in cellular organization, yet their molecular-scale interactions with membranes remain poorly understood. Here, we use surface-enhanced infrared absorption spectroscopy (SEIRAS) to quantify the secondary structure of poly-GR (glycine-arginine) inside condensates in contact supported lipid bilayers. Amide I SEIRAS provides a surface-sensitive measure of the peptide backbone conformation at the membrane-condensate interface. Results show that neutral POPC bilayers preserve the {beta}-sheet rich organization of the bulk condensate, whereas negatively charged POPC/POPS bilayers reduce {beta}-sheet content, and enhanced {beta}-turn formation, accompanied by perturbations of the lipid headgroups. These results demonstrate that membrane charge modulates condensate secondary structure, hydration, and interfacial behavior, providing molecular-level insight into electrostatic regulation of condensate organization at the membrane-water interface. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/726873v1_ufig1.gif" ALT="Figure 1"> View larger version (112K): org.highwire.dtl.DTLVardef@9d9e27org.highwire.dtl.DTLVardef@1fa3fe4org.highwire.dtl.DTLVardef@78bcceorg.highwire.dtl.DTLVardef@b3a2ae_HPS_FORMAT_FIGEXP M_FIG C_FIG