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.

Ventral stress fibers induce plasma membrane deformation in human fibroblasts.

Interactions between the actin cytoskeleton and the plasma membrane are important in many eukaryotic cellular processes. During these processes, actin structures deform the cell membrane outward by applying forces parallel to the fiber's major axis (as in migration) or they deform the membrane inward by applying forces perpendicular to the fiber's major axis (as in the contractile ring during cytokinesis). Here we describe a novel actin-membrane interaction in human dermal myofibroblasts. When labeled with a cytosolic fluorophore, the myofibroblasts displayed prominent fluorescent structures on the ventral side of the cell. These structures are present in the cell membrane and colocalize with ventral actin stress fibers, suggesting that the stress fibers bend the membrane to form a "cytosolic pocket" that the fluorophores diffuse into, creating the observed structures. The existence of this pocket was confirmed by transmission electron microscopy. While dissolving the stress fibers, inhibiting fiber protein binding, or inhibiting myosin II binding of actin removed the observed pockets, modulating cellular contractility did not remove them. Taken together, our results illustrate a novel actin-membrane bending topology where the membrane is deformed outward rather than being pinched inward, resembling the topological inverse of the contractile ring found in cytokinesis.