Shape-morphing living composites

Abstract

This work establishes a means to exploit genetic networks to create living synthetic composites that change shape in response to specific biochemical or physical stimuli. Baker's yeast embedded in a hydrogel forms a responsive material where cellular proliferation leads to a controllable increase in the composite volume of up to 400%. Genetic manipulation of the yeast enables composites where volume change on exposure to l-histidine is 14× higher than volume change when exposed to d-histidine or other amino acids. By encoding an optogenetic switch into the yeast, spatiotemporally controlled shape change is induced with pulses of dim blue light (2.7 mW/cm²). These living, shape-changing materials may enable sensors or medical devices that respond to highly specific cues found within a biological milieu.

Fig. 1. Controlled expansion of polyacrylamide gels by proliferation of yeast.

(A) Schematic of shape change in living composites. In YPD, yeast proliferate and cause expansion in the polymer matrix. (B) Optical micrographs of a living composite before and after growth in medium. Scale bar, 30 μm. (C) Macroscopic expansion of a living composite gel with 6 wt % yeast. Scale bar, 7 mm. (D) Area change over time of a sample with 6 wt % yeast in the presence of medium with and without glucose. (E) Photopatterning process of a living composite. (F) Fluorescence images of a living composite after UV patterning (top) and after incubation in YPD (bottom). Scale bar, 10 mm. Topography of an initially flat living composite after exposure to YPD (right). Scale bar, 5 mm. Each data point represents the mean (n = 3), and error bars represent SD. Trend lines are only intended to guide the eye.

Fig. 2. Shape change of living composites can be controlled.

(A) Volume and mass change of living composites as a function of yeast content. (B) Compressive modulus and volume change as a function of cross-linker content. (C) Flat disk exposed to spatially patterned UV light (left) in a 3-mm-wide ring pattern (inset). After incubation in medium, a hat-like structure with positive Gaussian curvature is observed (center, right). Scale bar, 5 mm. (D) Flat disk exposed to spatially patterned UV light (left) in a 6-mm inner circle (inset). Upon incubation in medium, a saddle-like structure with negative Gaussian curvature is observed (center, right). Scale bar, 5 mm. Each data point represents the mean (n = 3), and error bars represent SD. Trend lines are only intended to guide the eye.

Fig. 3. Genetic engineering enables controlled composite response to specific cues.

(A)Deletion of the HIS3 gene results in failure to proliferate in medium lacking histidine. (B) Schematic of a UV-patterned living composite with growth triggered by the amino acid l-histidine. (C) UV-patterned living composites with auxotrophic yeast do not substantially change in shape in medium lacking l-histidine. Shape change into a helical structure after incubation in medium containing l-histidine. Scale bar, 10 mm. (D) Volume change over time for auxotrophic living composites before and after l-histidine exposure. (E) Volume change over time for auxotrophic living composites incubated in medium lacking histidine, with d-histidine, or with l-histidine. (F) Schematic of a living microfluidic device where the composites forming the channels indicated in green contain living auxotrophic yeast. (G) Fluorescence image of fluid traversing the microfluidic device before exposure to medium (top left). Scale bar, 10 mm. Fluorescence image of fluid traversing the microfluidic device after medium containing l-histidine flows for 48 hours through the channels. Topography of a living channel before and after (color scale, 0 to 0.3 mm) growth (bottom). Scale bar, 1 mm. Each data point represents the mean (n = 3), and error bars represent SD. Trend lines are only intended to guide the eye.

Fig. 4. Genetic engineering enables optogenetic control of shape change.

(A) Schematic of a light sensitive yeast two-hybrid. Blue light induces expression of HIS3 and lacZ reporters by inducing conformational changes in CRY2 to favor interaction with CIB1. Reporter genes are transcribed by recruitment of the Gal4 activation domain (AD). (B) β-Galactosidase assays of an auxotrophic strain lacking CIB1 (negative control), a strain not auxotrophic for l-histidine in the dark (positive control), and the auxotrophic strain depicted in (A) (experimental). (C) Schematic of a living composite irradiated with blue light in growth medium lacking l-histidine. (D) Volume change of living composites with experimental yeast irradiated with blue light or kept in the dark. Scale bar, 5 mm. (E) Volume change of living composites with each yeast strain when exposed to blue light or kept in the dark. (F) Patterned photoresponsive living composite with the experimental yeast strain in medium lacking l-histidine where blue light is first targeted on the left side and then the right side. Scale bar, 10 mm. Each data point represents the mean (n = 3), and error bars represent SD.