Phase Separation and Nanodomain Formation in Hybrid Polymer/Lipid Vesicles

Abstract

International audienceHybrid polymer/lipid large unilamellar vesicles (LUVS) were studied by small angle neutron scattering (SANS), time-resolved Forster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM). For the first time in hybrid vesicles, evidence for phase separation at the nanoscale was obtained, leading to the formation of stable nanodomains enriched either in lipid or polymer. This stability was allowed by using vesicle-forming copolymer with a membrane thickness dose to the lipid bilayer thickness, thereby minimizing the hydrophobic mismatch at the domain periphery. Hybrid giant unilamellar vesicles (GUVs) with the same composition have been previously shown to be unstable and susceptible to fission, suggesting a role of curvature in the stabilization of nanodomains in these structures

Magneto‐Thermal Release from Nanoscale Unilamellar Hybrid Vesicles

“…Both Nallani and co‐workers and Kroeger and co‐workers have previously reported that LUVs can be formed that co‐localize lipids and block co‐polymers in each vesicle. However, the existence of nanoscale phase separation could only be demonstrated recently by Le Meins and co‐workers in triblock PEO‐PDMS‐PEO/phospholipid LUV, which show phase separation at all temperatures, using SANS and FRET . Our measurements address PBD‐ b ‐PEO/phopspholipid LUVs, for which lipid domain formation in GUVs only occur below the lipid T m .…”

“…Given that we have shown that USPIONs can efficiently be loaded at high weight fraction by solvent inversion into both liposomes and PBD‐ b ‐PEO polymersomes (above and ), the most likely reason for the reduced fraction of released cargo is an inhomogeneous distribution of lipid between vesicles. Inhomogeneous distribution of lipids in hybrid LUVs was recently observed using flow cytometry by Le Meins and co‐workers for triblock copolymer and lipids both above and below the lipid T m . Domains that are large enough to yield release will not form at too low lipid fractions in the individual vesicles …”

“…This might be influencedb yt hat small GUVs approach the resolution limit of the fluorescence microscope.R aft formation on the nanoscale has been reported using super-resolutiont echniques for purely lipid membranes. [40] The translation of the existence of lipid domains observedf or micron-sized vesiclest on anoscale hybrid vesicles was recently inferred based on neutrons cattering and FRET experiments on PDMS-b-PEO/phospholipid LUVs, [41] but they have to date not been directly visualized for lipid/diblock copolymer hybrid vesicles.…”

“…Both Nallani and co-workers [29] and Kroeger and co-workers [46] have previously reported that LUVs can be formed that co-localize lipids and block co-polymers in each vesicle.H owever,t he existence of nanoscale phase separation could only be demonstrated recently by Le Meins and co-workers in triblock PEO-PDMS-PEO/ phospholipid LUV,w hichs how phase separation at all temperatures,u sing SANS and FRET. [41] Our measurements address PBD-b-PEO/phopspholipidL UVs, for which lipid domain formation in GUVs only occur below the lipid T m .T hat magneto-thermally actuatedr eleaseo ccurs showst hat in am ajority of these vesicles such lipid domains exist, and that these can be employed in combination with USPION to augment the vesicles with magnetic responsiveness. Only in al ipid domain can we observe the phase transition required for increased permeability,s ince the collective order transition from gel to liquid phase could not take place if the lipids were distributed throughout the polymerm embrane.…”

Barcoding biological reactions with DNA-functionalized vesicles

“…[43,[51][52][53][54][55][56][57][58] Understanding how to harness biophysical properties of bilayer membranes to expand their functionality beyond containment alone is an important step in the design of artificial cellular systems. Domains have been recapitulated and characterized in both lipid and polymer systems.…”