Jammed agarose microgel as 3D media
Jammed microgels are a promising class of biomaterials well-suited for 3D cell culture, tissue bioengineering, and 3D bioprinting. However, existing protocols for fabricating such microgels either involve complex synthesis steps, long preparation times, or polyelectrolyte hydrogel formulations that sequester ionic elements from the cell growth media. Hence, there is an unmet need for a universally biocompatible, high-throughput, and widely accessible manufacturing process. We address these demands by introducing a rapid, high-throughput, and remarkably straightforward method to synthesize jammed microgels composed of flash-solidified agarose granules directly prepared in a culture medium of choice. Read more about this work here.
Morphological instability and roughening of growing 3D bacterial colonies
The morphogenesis of two-dimensional bacterial colonies has been well studied. However, little is known about the colony morphologies of bacteria growing in three dimensions, despite the prevalence of three-dimensional environments (e.g., soil, inside hosts) as natural bacterial habitats. Using experiments on bacteria in granular hydrogel matrices, we find that dense multicellular colonies growing in three dimensions undergo a common morphological instability and roughen, adopting a characteristic broccoli-like morphology when they exceed a critical size. Analysis of a continuum “active fluid” model of the expanding colony reveals that this behavior originates from an interplay of competition for nutrients with growth-driven colony expansion, both of which vary spatially. These results shed light on the fundamental biophysical principles underlying growth in three dimensions. Read more about this work here.
Chemotactic smoothing of collective migration
Collective migration—the directed, coordinated motion of many self-propelled agents—is a fascinating emergent behavior exhibited by active matter with functional implications for biological systems. However, how migration can persist when a population is confronted with perturbations is poorly understood. Here, we address this gap in knowledge through studies of bacteria that migrate via directed motion, or chemotaxis, in response to a self-generated nutrient gradient. We find that bacterial populations autonomously smooth out large-scale perturbations in their overall morphology, enabling the cells to continue to migrate together. This smoothing process arises from spatial variations in the ability of cells to sense and respond to the local nutrient gradient—revealing a population-scale consequence of the manner in which individual cells transduce external signals. Altogether, our work provides insights to predict, and potentially control, the collective migration and morphology of cellular populations and diverse other forms of active matter. Read more about this work here.
Bacterial Chemotaxis in Porous Media
Chemotactic migration of bacteria—their ability to direct multicellular motion along chemical gradients—is central to processes in agriculture, the environment, and medicine. However, studies are typically performed in bulk liquid, despite the fact that most bacteria inhabit heterogeneous porous media such as soils, sediments, and biological gels. By using direct visualization and 3D bioprinting, we find that cellular chemotaxis drives collective migration while confinement in a porous medium fundamentally alters chemotactic migration in two ways. First, cells bias their motion through a different primary mechanism in confinement than in bulk liquid. Second, confinement markedly alters the dynamics and morphology of the migrating population—features that can be described by a continuum model, but only when standard motility parameters are substantially altered from their bulk liquid values. Our work thus provides a framework to predict and control the migration of bacteria, and active matter in general, in heterogeneous environments. Read more about this work here.