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

Abstract

In the emerging field of hybrid polymer/lipid vesicles, relatively few copolymers have been evaluated regarding their ability to form these structures and the resulting membrane properties have been scarcely studied. Here, we present the synthesis and self-assembly in solution of poly(dimethylsiloxane)-block-poly(ethylene oxide) diblock copolymers (PDMS-b-PEO). A library of different PDMS-b-PEO diblock copolymers was synthesized using ring-opening polymerization of hexamethylcyclotrisiloxane (D3) and further coupling with PEO chains via click chemistry. Self-assembly of the copolymers in water was studied using Dynamic Light Scattering (DLS), Static Light Scattering (SLS), Small Angle Neutron Scattering (SANS), and Cryo-Transmission Electron Microscopy (Cryo-TEM). Giant polymersomes obtained by electroformation present high toughness compared to those obtained from triblock copolymer in previous studies, for similar membrane thickness. Interestingly, these copolymers can be associated to phospholipids to form Giant Hybrid Unilamellar Vesicles (GHUV); preliminary investigations of their mechanical properties show that tough hybrid vesicles can be obtained.

Keywords: Block copolymer; Giant Hybrid Unilamellar Vesicles; Micropipette; Phospholipid; self-assembly.

Scheme 1

General synthesis procedure to obtain PDMS-b-PEO copolymers.

Figure 1

DLS at 90° with size distribution by intensity (plain lines) and autocorrelation function (dashed lines) of polymersomes made of: Si₁₄EO₈ (a); Si₂₃EO₁₃ (b); Si₂₇EO₁₇ (c); and Si₃₆EO₂₃ (d).

Figure 2

Relaxation frequency versus q² for Si₂₃EO₁₃ (red squares), Si₂₇EO₁₇ (blue squares), and Si₃₆EO₂₃ (green squares).

Figure 3

Multi-angle and multi-concentration Guinier plot showing intensity measured (white squares) and extrapolation to zero concentration and zero angle (colored squares) for polymersomes made from: Si₂₃EO₁₃ (a); Si₂₇EO₁₇ (b); and Si₃₆EO₂₃ (c).

Figure 4

(a–d) Cryo-TEM images of polymersomes obtained for the different copolymers: (a) polymersomes obtained from Si₁₄EO₈; (b) polymersomes obtained from Si₂₃EO₁₃; (c) polymersomes obtained from Si₂₇EO₁₇; and (d) polymersomes obtained from Si₃₆EO₂₃. Inserts show zooms on single polymersomes with the measured membrane thickness. (e) SANS curves of the four diblocks. Black lines represent the best fits using the polydisperse vesicle model.

Figure 5

Membrane thickness versus PDMS molar mass plot. Membrane thickness was extracted from the SANS fits. It obeys a power law with an exponent value close to 0.5. Error bars represent the membrane thickness (Log-normal) distribution.

Figure 6

(a) LSCM (laser scanning confocal microscopy) image of GUVs under tension exerted by the micropipette. Intensity in the fluorescence green channel from PDMS-NBD and transmission channel were merged. R_v, R_p, and ΔL indicate vesicle radius, pipette radius, and variation of the tongue projection length, respectively. (b) Tension versus areal strain plot showing the typical curves obtained for GUVs composed of: POPC (grey dots), Si₂₃EO₁₃ (red dots), Si₂₇EO₁₇ (blue dots), and Si₃₆EO₂₃ (green dots). Fit of the data are represented in dotted black lines. The dotted colored lines indicate the lysis strain in the x-axis and the lysis stress in the y-axis.

Figure 7

Cohesive energy density versus membrane thickness for GUV obtained from diblock PDMS-b-PEO copolymers. The grey circle illustrates a typical value of liposomes.

Figure 8

Confocal images obtained from GHUVs made of Si₂₇EO₁₇ mixed with 10 wt.% POPC. Images were obtained from a z-stack of different focal plans: (a) green channel from PDMS-NBD; (b) red channel from PE-Rhodamine; and (c) merged channels.

Figure 9

Typical micropipette aspiration curves obtained for GHUVs composed of Si₂₇EO₁₇ with 10% w/w POPC (orange circles). Properties of pure polymersomes (Si₂₇EO₁₇, green circles) and pure liposomes (POPC, red circles) are displayed for comparison. Dotted lines indicate the lysis strain in the x-axis and the lysis stress in the y-axis.