Multiple patterns of polymer gels in microspheres due to the interplay among phase separation,wetting, and gelation

We report the spontaneous patterning of polymer microgels by confining a polymer blend within microspheres. A poly(ethylene glycol) (PEG) and gelatin solution was confined inside water-in-oil (W/O) microdroplets coated with a layer of zwitterionic lipids: dioleoylphosphatidylethanolamine (PE) and dioleoylphosphatidylcholine (PC). The droplet confinement affected the kinetics of the phase separation, wetting, and gelation after a temperature quench, which determined the final microgel pattern. The gelatin-rich phase completely wetted to the PE membrane and formed a hollow microcapsule as a stable state in the PE droplets. Gelation during phase separation varied the relation between the droplet size and thickness of the capsule wall. In the case of the PC droplets, phase separation was completed only for the smaller droplets, wherein the microgel partially wetted the PC membrane and had a hemisphere shape. In addition, the temperature decrease below the gelation point increased the interfacial tension between the PEG/gelatin phases and triggered a dewetting transition. Interestingly, the accompanying shape deformation to minimize the interfacial area was only observed for the smaller PC droplets. The critical size decreased as the gelatin concentration increased, indicating the role of the gel elasticity as an inhibitor of the deformation. Furthermore, variously patterned microgels with spherically asymmetric shapes, such as discs and stars, were produced as kinetically trapped states by regulating the incubation time, polymer composition, and droplet size. These findings demonstrate a way to regulate the complex shapes of microgels using the interplay among phase separation, wetting, and gelation of confined polymer blends in microdroplets.The regulation of the 3D shapes of biopolymer gels at the mesoscale has numerous applications in the biomedical, cosmetic, and food materials industries, among others (1). Recently, top-down and bottom-up approaches have been reported to control the mesoscopic patterns of polymer gels. For example, photolithography and two-photon polymerization allow the regulation of gel patterns at the mesoscale (2–4). The advanced design of the molecules enables polymerization with a self-assembly and produces nonspherical microgels: spherical particles with a cavity, capsules, and cubic particles (5–7). However, these methods require highly specialized equipment and are generally difficult to adapt for biopolymer gels.Dynamical coupling between phase separation and sol–gel transition in polymer blends has also been investigated for the spontaneous formation of spherical microgels and a porous gel (8, 9). Ma et al. (10) and Choi et al. (11) confined aqueous two-phase systems (ATPSs) in microdroplets and fabricated microgels by selective polymerization. In such a confined space, phase separation accompanies wetting of a polymer to the substrate (12–15). Although the selective polymerization of phase-separated polymers in microdroplets has a great potential to produce variously shaped microgels, the dynamical coupling among the phase separation, wetting, and gelation of polymers in a confined space remains unclear (16). If it was better understood, the shapes of polymer microgels could be regulated in a self-organized manner.In the present work, we used gelatin, one of the most popular biopolymer gels, and poly(ethylene glycol) (PEG) as the desolvating agent because PEG leads to phase separation for various biopolymers, such as proteins and DNA (17). The gelatin/PEG solution was confined in water-in-oil (W/O) microdroplets coated by a lipid layer, wherein the phase separation and sol–gel transition of the gelatin occur with a decrease in the temperature (18–20). This process led to gelation after and during the phase separation in the presence of the interactions between the polymers and lipid membranes. We analyzed the pattern formation of the gelatin microgel as a function of the temperature history, droplet size, and polymer composition. We found that variously shaped microgels appeared as stable states and kinetically trapped states. These findings yield a method to regulate the shapes of polymer microgels using the interplay among the interfacial tensions, elastic properties of the gels, and interactions between the polymers and the surfaces of the droplets.