Phase Changes in Mixed Lipid/Polymer Membranes by Multivalent Nanoparticle Recognition

Abstract

Selective addressing of membrane components in complex membrane mixtures is important for many biological processes. The present paper investigates the recognition between multivalent surface functionalized nanoparticles (NPs) and amphiphilic block copolymers (BCPs), which are successfully incorporated into lipid membranes. The concept involves the supramolecular recognition between hybrid membranes (composed of a mixture of a lipid (DPPC or DOPC), an amphiphilic triazine-functionalized block copolymer TRI-PEO13-b-PIB83 (BCP 2), and nonfunctionalized BCPs (PEO17-b-PIB87 BCP 1)) with multivalent (water-soluble) nanoparticles able to recognize the triazine end group of the BCP 2 at the membrane surface via supramolecular hydrogen bonds. CdSe-NPs bearing long PEO47-thymine (THY) polymer chains on their surface specifically interacted with the 2,4-diaminotriazine (TRI) moiety of BCP 2 embedded within hybrid lipid/BCP mono- or bilayers. Experiments with GUVs from a mixture of DPPC/BCP 2 confirm selective supramolecular recognition between the THY-functionalized NPs and the TRI-functionalized polymers, finally resulting in the selective removal of BCP 2 from the hybrid vesicle membrane as proven via facetation of the originally round and smooth vesicles. GUVs (composed of DOPC/BCP 2) show that a selective removal of the polymer component from the fluid hybrid membrane results in destruction of hybrid vesicles via membrane rupture. Adsorption experiments with mixed monolayers from lipids with either BCP 2 or BCP 1 (nonfunctionalized) reveal that the THY-functionalized NPs specifically recognize BCP 2 at the air/water interface by inducing significantly higher changes in the surface pressure when compared to monolayers from nonspecifically interacting lipid/BCP 1 mixtures. Thus, recognition of multivalent NPs with specific membrane components of hybrid lipid/BCP mono- and bilayers proves the selective removal of BCPs from mixed membranes, in turn inducing membrane rupture. Such recognition events display high potential in controlling permeability and fluidity of membranes (e.g., in pharmaceutics).

Large and Giant Unilamellar Vesicle(s) Obtained by Self-Assembly of Poly(dimethylsiloxane)-b-poly(ethylene oxide) Diblock Copolymers, Membrane Properties and Preliminary Investigation of Their Ability to Form Hybrid Polymer/Lipid Vesicles

“…Thus far, relatively little information is available about the structure, chemical nature, and molar mass of copolymers that could mix ideally with phospholipids. Most commonly, poly(butadiene) [3][4][5][6][7][8][9][10][11][12] and poly(dimethylsiloxane) [13][14][15][16][17][18][19][20] have been used as hydrophobic block, while studies with poly(isobutene) [21][22][23], poly(caprolactone) [24,25], poly(isoprene) [26], and poly(laurylacrylate) [27] have also been reported. Poly(ethylene oxide) is by far the most used hydrophilic block, although few studies report the use of hydrophilic thermo-responsive blocks such as poly(2-isopropyl-2-oxazoline) [28] and poly(ethylene glycoldiacrylate) [27].…”

The combination of block copolymers and phospholipids to form giant hybrid unilamellar vesicles (GHUVs) does not systematically lead to “intermediate” membrane properties

“…These emerging systems have already been the subject of two reviews. 2,3 A significant number of studies have focused on their use in different fields, such as drug delivery [4][5][6][7] , drug targeting, 8 nanoreactors, 7,9,10 biomolecular recognition and interaction with nanoparticles [11][12][13][14] , or their interaction with biological media. 15 So far, only a relatively moderate part of the work published on the subject has focused on the selfassembly problematic: how can we modulate the phase separation process during the self-assembly, preventing formation of separated liposomes and polymersomes, and obtain membranes with lipid domains of controlled size?…”

Constraining Polymers into β-Turns: Miscibility and Phase Segregation Effects in Lipid Monolayers

“…(Figure 4a,b), show randomly distributed cylindrical PIB domains with a dominating height of~15 nm out of the plane lipid monolayer (LC domain) or out of round shaped plateaus (height 5 nm, due to partial squeeze out of the PIB), thus displaying three different domains. These cylindrical structures are in fact disc-like domains considering their dimensions, whereby their height correlates with a single-folded PIB chain [28,48]. Also, the phase image (Figure 4c) shows the three different phases, proving that the PIB discs are squeezed out (dark: soft) of the PIB rich plateau, which are surrounded by the LC phase of the lipid (bright: hard, due to the small thickness and the underlying silicon).…”

“…In the past, we have demonstrated studies [6][7][8][9]24,[26][27][28][29][30][31][32][33][34][35], where mixed polymer/lipid monoand bilayers had been investigated, both on Langmuir-monolayer systems [28] or within bilayer membranes [24,27,29,34], demonstrating that functionality and control of such domains can be achieved within the mono-and bilayer systems [27]. Thus functional biological recognition of gangliosides can be achieved specifically within/outside the lipid-domains [24], nanoparticles can be enriched selectively within the polymer domains [9,30,31,33], and supramolecular recognition leads to macroscopic effects on the vesicular surfaces via budding and fission of the lipid membrane [28].…”

“…Thus functional biological recognition of gangliosides can be achieved specifically within/outside the lipid-domains [24], nanoparticles can be enriched selectively within the polymer domains [9,30,31,33], and supramolecular recognition leads to macroscopic effects on the vesicular surfaces via budding and fission of the lipid membrane [28].…”