The living interface between synthetic biology and biomaterial design

Abstract

Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. We highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to 'living' materials that sense and respond based on the reciprocal interactions between materials and embedded cells.

Figure 1|. Programmability of synthetic biology.

a, The heart of synthetic biology rests on our capability to program cells as information processing units for sensing a variety of inputs and produce discrete actionable outputs. Advances in information processing have been inspired by computational operations and algorithms and more recently propelled by the use of CRISPR-based networks for information recording. b, Artificial / Synthetic cells made from basic biological building blocks and incorporating transcription (TX) and translation (TL) machineries can recapitulate salient features of living cells such as basic chemical signaling, transcriptional dynamics, intracellular organization, and cytoskeleton organization. c, Recent advances in mammalian synthetic biology are focused on engineering receptors to allow customized sensing and response behaviors. This leverages the coupling of a desired input to a transcription factor to alter gene expression. d, Opportunities for automation in the design-build-test-learn cycle of synthetic biology. To date, partial autonomy exists for portions of the cycle while bridging gaps in the connections and curation of machine-interpretable information are emerging. Supplying goals and interpreting the results based on domain knowledge is an important function of the researcher and will be last to be automated. Figure d is adapted from Ref .

Figure 2|. The design space for biomaterials.

a, Current design paradigm involves selection of biomaterials, crosslinking type, cell-adhesion ligand type and density, specification of void space, inclusion of elastic fibers, and multi-phase materials in order to control mechanical properties (stiffness, viscoelasticity, nonlinear elasticity, plasticity), biological signaling, and micro-scale architecture of the resulting biomaterial. b, Recent advances in biomaterials where stimuli such as light, temperature, magnetic fields, and biomechanical signals can induce changes in the properties of the biomaterial. c, The combination of high-throughput biomaterials production and omics-type measurements of biomaterial properties with the application of machine learning to identify design rules, may pave the way towards next generation biomaterials. Heatmap in Figure 2c is from Ref .

Figure 3|. Using synthetic biology to fabricate biomaterials with tailored properties toward ‘living’ materials systems.

a, Biomaterials inspired, derived, or produced by natural systems, including proteins, polysaccharides, and DNA, are being used in a variety of applications. In particular, cellular systems are being engineered for the production of materials. An exciting direction for merging synthetic biology and biomaterials is to create ‘living’ materials that not only instruct the cells, but where the cells in turn modulate the material properties. b, Schematic of cells programmed with biological circuitry. Stimulatory molecules (green circles) induce stimulatory receptor dimerization which causes the cell to perform a specific task (e.g., fluoresce green and secrete material with an inhibitory molecule). Similarly, inhibitory molecules (synthesized material with a red circle) cause inhibitory receptors to dimerize, signaling the cell to stop fluorescing and producing material. c, Schematic of SynBricks. Cells programmed with stimulatory and inhibitory biological feedback can be encapsulated in sacrificial hydrogel scaffolds with stimulatory molecules, causing resident cells to glow green and replace the hydrogel with calcium carbonate (raw material of bricks) tagged with inhibitory molecules. Once the inhibitory molecule concentration surpasses a threshold, cells will stop fluorescing and producing SynBrick material.