Building Spatial Synthetic Biology with Compartments, Scaffolds, and Communities

Abstract

Traditional views of synthetic biology often treat the cell as an unstructured container in which biological reactions proceed uniformly. In reality, the organization of biological molecules has profound effects on cellular function: not only metabolic, but also physical and mechanical. Here, we discuss a variety of perturbations available to biologists in controlling protein, nucleotide, and membrane localization. These range from simple tags, fusions, and scaffolds to heterologous expression of compartments and other structures that confer unique physical properties to cells. Next, we relate these principles to those guiding the spatial environments outside of cells such as the extracellular matrix. Finally, we discuss new directions in building intercellular organizations to create novel symbioses.

Figure 1.

Potential benefits of compartmentalization (with gray circles representing intracellular compartments). (A) Concentration of enzymes. (B) Increased concentration of intermediates through a selectively permeable diffusion barrier. (C) Maintenance of a chemical microenvironment essential for enzymatic function. (D) Protection of enzymes from molecules from deactivators or competitors. (E) Isolation of toxic enzymes of intermediates from the cell.

Figure 2.

Transmission electron micrographs (TEMs) of cellular compartments, scaled to their relative size. (A) Lumazine synthase (Zhang et al. 2006a). (B) Encapsulin (Sutter et al. 2008). (C) Vaults (Kedersha and Rome 1986). (D) Magnetosomes near the cell membrane (Komeili et al. 2006). (E) Calveolae: budding from the cell membrane is indicated with an arrow (Walser et al. 2012). (F) Gas vesicles (Pfeifer 2012). (G) α carboxysomes: arrows indicate vertexes, triangle indicates RuBisCO (Schmid et al. 2006). Scale bar, 100 µm.