Cross-Linked Collidosomes Exhibit pH-Induced Morphogenesis

We present a biologically-inspired strategy for developing functional materials with the capacity to morph.  We utilized local mechanical cues to affect global shape changes in a network of colloids called colloidosomes.  We used pH-responsive calcium alginate particles (CAPs) that were ionically cross-linked with either 2% or 20% w/v CaCl₂.  CAPs cross-linked with 2% w/v CaCl₂ exhibited approximately twice the swelling of particles made with 20% CaCl₂.  Predictive modeling showed that localization of responsive particles induced non-spherical shape changes.  To verify the simulations, CAPs were dispersed into the aqueous phase in a 1:1 ratio of 2% and 20% CaCl₂ while mineral oil was used in the oil phase.  Colloidosomes were fabricated via a w/o emulsion stabilized by CAPs.  Exposed carboxyl groups on the CAPs were cross-linked using a carbodiimide coupling reaction.  We explored ethylene diamine (ED), butane-1,4-diamine (BD), and hexane-1,6-diamine (HD) for achieving chemically cross-linked colloidosomes with varying chain lengths between colloids.  Colloidosomes were then swollen in phosphate buffer at pH 7.4 for 6 hr, and colloidosome morphology was observed.  Uncross-linked colloidosomes did not increase in size or deviate from a spherical shape after swelling.  Although cross-linked colloidosomes with ED and BD resulted in increases in the colloidosome diameter after swelling, the colloidosomes remained spherical.  Significant colloidosome shape changes occurred when HD was used to tether CAPs together due to an increase in chain length between cross-links.  Approximately 80% of the intact colloidosome population cross-linked with HD exhibited large, non-spherical deformations.  The formation of heart, flower, and dumbbell shapes were observed.  We quantified the extent of global shape deformation by calculating the ratio of the surface area after swelling to the initial surface area.  Colloidosomes cross-linked with HD had a statistically significant change in area as compared to colloidosomes cross-linked with ED.  Our findings suggest that local mechanical stresses can generate new colloidosome isoforms, resembling morphogenesis in biology.  We demonstrated that coordinated networks of heterogeneous subunits may be used to design programmable materials.  This work may be useful in tissue engineering, drug delivery and sensors where a nonlinear response is desired.