Towards a Better Raft Model: Modulated Phases in the 4-Component Bilayer Mixture, DSPC/DOPC/POPC/CHOL

Abstract

Liquid-liquid coexistence (Ld+Lo) within the DSPC/DOPC/POPC/CHOL mixture displays a nanoscopic-to-macroscopic transition of the phase domains as POPC is replaced by DOPC. Previously, we have shown that the nano-to-macro transition goes through a modulated phase regime, where patterned liquid-liquid phase morphologies were observed on giant unilamellar vesicles (GUVs). Here, we provide a more detailed investigation of the modulated phase regime along two different thermodynamic tielines within the Ld+Lo region of this 4-component mixture. Using fluorescence microscopy on GUVs, we found that modulated phases occur at relatively narrow DOPC/(DOPC+POPC) ratios along one tieline. This “modulated phase window” is greatly altered when cholesterol concentration is increased. Furthermore, when phase connectivity (percolation) changes, domain patterns also change. Monte Carlo simulations using a competing interactions model of line tension and curvature energies reproduced the patterns observed on GUVs. Sufficiently low line tension and sufficiently high bending moduli are required to generate stable modulated phases in the system examined. By tuning lipid composition, both domain size and morphology can be altered drastically within a narrow composition space. A possible mechanism for cells to reorganize plasma membrane compartmentalization is by tuning local membrane composition.View Large Image | View Hi-Res Image | Download PowerPoint Slide