Microbial models of development: Inspiration for engineering self-assembled synthetic multicellularity.

While the field of synthetic developmental biology has traditionally focused on the study of the rich developmental processes seen in metazoan systems, an attractive alternate source of inspiration comes from microbial developmental models. Microbes face unique lifestyle challenges when forming emergent multicellular collectives. As a result, the solutions they employ can inspire the design of novel multicellular systems. In this review, we dissect the strategies employed in multicellular development by two model microbial systems: the cellular slime mold Dictyostelium discoideum and the biofilm-forming bacterium Bacillus subtilis. Both microbes face similar challenges but often have different solutions, both from metazoan systems and from each other, to create emergent multicellularity. These challenges include assembling and sustaining a critical mass of participating individuals to support development, regulating entry into development, and assigning cell fates. The mechanisms these microbial systems exploit to robustly coordinate development under a wide range of conditions offer inspiration for a new toolbox of solutions to the synthetic development community. Additionally, recreating these phenomena synthetically offers a pathway to understanding the key principles underlying how these behaviors are coordinated naturally.

Cell cycle-dependent endocytosis of DNA-wrapped single-walled carbon nanotubes by neural progenitor cells.

While exposure of C17.2 neural progenitor cells (NPCs) to nanomolar concentrations of carbon nanotubes (NTs) yields evidence of cellular substructure reorganization and alteration of cell division and differentiation, the mechanisms of NT entry are not understood. This study examines the entry modes of (GT)20 DNA-wrapped single-walled carbon nanotubes (SWCNTs) into NPCs. Several endocytic mechanisms were examined for responsibility in nanomaterial uptake and connections to alterations in cell development via cell-cycle regulation. Chemical cell-cycle arrest agents were used to synchronize NPCs in early G1, late G1/S, and G2/M phases at rates (>80%) aligned with previously documented levels of synchrony for stem cells. Synchronization led to the highest reduction in SWCNT internalization during the G1/S transition of the cell cycle. Concurrently, known inhibitors of endocytosis were used to gain control over established endocytic machineries (receptor-mediated endocytosis (RME), macropinocytosis (MP), and clathrin-independent endocytosis (CIE)), which resulted in a decrease in uptake of SWCNTs across the board in comparison with the control. The outcome implicated RME as the primary mechanism of uptake while suggesting that other endocytic mechanisms, though still fractionally responsible, are not central to SWCNT uptake and can be supplemented by RME when compromised. Thereby, endocytosis of nanomaterials was shown to have a dependency on cell-cycle progression in NPCs.