Published on Web 11/10/2004
Shape-Tunable Polymer Nodules Grown from Liposomes via Ring-Opening
Metathesis Polymerization
Nathalie Jarroux,†,‡ Patrick Keller,†, Anne-Franc¸oise Mingotaud,*,§ Christophe Mingotaud,§ and
Ce´cile Sykes*,†
Laboratoire de Physicochimie “Curie”, Institut Curie, UMR 168, 11 rue Pierre et Marie Curie,
75231 Paris Cedex 05, France, Laboratoire “Mate´riaux Polyme`res aux Interfaces”, UMR 7581, UniVersite´ d’EVry
Val d’Essonne, UFR Sciences Fondamentales et Applique´es, Bd. F. Mitterrand, 91025 EVry Cedex, France,
Laboratoire des Interactions Mole´culaires et Re´actiVite´s Chimique et Photochimique, UMR 5623, UniVersite´ Paul
Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex, France, and Ferroelectric Liquid Crystals Material
Research Center, Department of Chemistry and Biochemistry, UniVersity of Colorado, Boulder, Colorado 80309
Received July 27, 2004; E-mail: cecile.sykes@curie.fr
Scheme 1
Polymerization in lyotropic phases is a quickly expanding
research area at the boundaries between various scientific domains
(colloid, polymer, material, and biomedical science). In particular,
the covalent assembly of the surfactants constituting the bilayers
of liposomes has been developed in the past two decades1-4 with
the motivation of creating vectors with potential applications in
drug delivery. Indeed, such a process confers strengthened me-
chanical properties to an initially soft and fluid surface. The reaction
3-phosphocholine (DOPC) and initiator 1 (in molar ratio close to
20) in CHCl3. The observed size of the liposomes was in the 1-4
is based on the use of unsaturated phospholipids forming the
liposome bilayers, and the polymerization reaction is usually of
µm range.
radical type and triggered photochemically. Another approach
The polymerization reaction occurred in a glovebox in the
consists of polymerizing lipophilic monomers (styrene mainly)
presence of an adequate amount of monomer 2 (5-norbornene-2
dissolved within the bilayers.5 In that case, the reaction results in
carboxylic acid) introduced via a syringe to a liposome solution
a polymer latex bead confined within the bilayer, which confers to
contained in a 1-mm-thick UV cell (quartz or glass). Monomer 2
the system the so-called “parachute architecture”.
was soluble at pH 8 in our solutions. The volume of monomer was
The strategy we develop here is different and reaches distinct
varied in order to modify the monomer/initiator ratio from 350 to
goals. We insert a catalyst at the liposome membrane so that
3500. The cell was sealed with a silicone stopper, mechanically
polymerization occurs on the external part of the liposome. As a
shaken, and removed from the glovebox to allow observation under
result, the polymerizing chain is pushed away from the surface.
the microscope.
For a monomer/initiator 2/1 ratio of 3500, polymer formation
The ultimate motivation for designing such a system is to biomimic
the motility of living organisms or objects that move inside cells
was observed after a couple of hours at the surface of the liposomes.
by polymerizing actin at their surface.6,7 The design of an abiotic
Decreasing the monomer/initiator ratio to 350 was sufficient to
experimental system able to produce a movement generated by
speed up polymerization for enabling shorter total reaction time
polymerization would be of great interest to physicists, chemists,
(typically 1 h). Calcium ions were substituted to sodium ions in
and biologists, as it would provide a new simplified, versatile, and
the aqueous phase in order to test whether physical cross-linking
of the polycarboxylated polymer chains via divalent cations could
reproducible system.
In this work, we investigated the ring-opening metathesis
induce changes in the shape, size, or compactness of the polymer
polymerization (ROMP) of norbornene-type monomers dissolved
nodules. Strikingly, substituting sodium in place of calcium (20
in the outer aqueous phase of liposomes in the bilayers of which a
mM calcium in Tris buffer adjusted to pH 8) accelerated the reaction
specially designed hydrophobic derivative of the Grubbs’ initiator
so that it occurred in less than 1 min. This marked effect on the
has been incorporated.8 We show that polymer nodules (up to 10
kinetics of the ROMP might be due to a kind of template effect
µm diameter) could be grown with a controllable shape at the
surface of liposomes, making of this system one of the most
productive surface-initiated polymerization systems described so
far. The initiator 1 (Scheme 1) was designed in order to have a
strong affinity for the hydrophobic part of vesicles and to maintain
the catalytic center along the bilayer during the polymerization that
occurred continuously at the surface of the liposome. It was obtained
using the method previously described9 (see Supporting Informa-
tion). Liposomes were prepared by rehydration in a pH 8 buffer of
a thin film obtained by drying a solution of 1,2-dioleoyl-sn-glycero-
around the calcium ion. However, in all experiments described here,
the addition of calcium did not result in any shape change. An
example of such an experiment is given in Figure 1, where a large
polymer mass is formed from several liposomes that are incorpo-
rated in the volume. Defocusing the microscope led to the
observation that the polymer mass partially wets the bottom surface
of the chamber, due to sedimentation.
To avoid this effect, we increased the density of the buffer
solution by adding sucrose (13% w/w, 330 mM) and observed
polymer nodules, the spherical shape of which was checked by
defocusing the microscope. All other experiments using monomer
2 were therefore carried out in tetraborate buffer containing calcium
ions at 0.1 mM, sodium ions at 19.9 mM, sucrose at 330 mM, and
a ratio monomer/initiator of 3500 as optimized conditions for
† Institut Curie.
‡ Universite´ d’Evry Val d’Essonne.
§ Universite´ Paul Sabatier.
University of Colorado.
9
15958
J. AM. CHEM. SOC. 2004, 126, 15958-15959
10.1021/ja045482j CCC: $27.50 © 2004 American Chemical Society