E Coli
e coli
3D Printing Cellular Communities: Mammalian Cells, Bacteria, And Beyond
While the motion and collective behavior of cells are well-studied on flat surfaces or in unconfined liquid media, in most natural settings, cells thrive in complex 3D environments. Bioprinting processes are capable of structuring cells in 3D and conventional bioprinting approaches address this challenge by embedding cells in bio-degradable polymer networks. However, heterogeneity in network structure and biodegradation often preclude quantitative studies of cell behavior in specified 3D architectures. Here, I will present a new approach to 3D bioprinting of cellular communities that utilizes jammed, granular polyelectrolyte microgels as a support medium. The self-healing nature of this medium allows the creation of highly precise cellular communities and tissue-like structures by direct injection of cells inside the 3D medium. Further, the transparent nature of this medium enables precise characterization of cellular behavior. I will describe two examples of my work using this platform to study the behavior of two different classes of cells in 3D. First, I will describe how we interrogate the growth, viability, and migration of mammalian cells—ranging from epithelial cells, cancer cells, and T cells—in the 3D pore space. Second, I will describe how we interrogate the migration of E. coli bacteria through the 3D pore space. Direct visualization enables us to reveal a new mode of motility exhibited by individual cells, in stark contrast to the paradigm of run-and-tumble motility, in which cells are intermittently and transiently trapped as they navigate the pore space; further, analysis of these dynamics enables prediction of single-cell transport over large length and time scales. Moreover, we show that concentrated populations of E. coli can collectively migrate through a porous medium—despite being strongly confined—by chemotactically “surfing” a self-generated nutrient gradient. Together, these studies highlight how the jammed microgel medium provides a powerful platform to design and interrogate complex cellular communities in 3D—with implications for tissue engineering, microtissue mechanics, studies of cellular interactions, and biophysical studies of active matter.
“Life in a Tight Spot: How Bacteria Move in Heterogeneous Media”
Bacterial motility is central to processes in agriculture, the environment, and medicine. While motility is typically studied in homogeneous environments, many bacterial habitats—e.g., soils, sediments, and biological gels/tissues—are heterogeneous porous media. Here, through studies of E. coli in transparent 3D porous media, we demonstrate that confinement in a heterogeneous medium fundamentally alters motility. In particular, we show how the paradigm of run-and-tumble motility is dramatically altered by pore-scale confinement, both for cells performing undirected motion and those performing chemotaxis, directed motion in response to a chemical stimulus. Our porous media also enable precisely structured multi-cellular communities to be 3D printed. Using this capability, we show how confinement-dependent chemotaxis enables populations to stabilize large-scale perturbations in their overall morphology. Together, our work thus reveals new principles to predict and control the behavior of bacteria, and active matter in general, in heterogeneous environments.