SignificanceBacteria live in surface-attached communities known as biofilms, where spatial structure is tightly linked to community function. We have developed a genetically encoded biofilm patterning tool (“Biofilm Lithography”) by engineering bacteria such that the expression of membrane adhesion proteins responsible for surface attachment is optically regulated. Accordingly, these bacteria only form biofilm on illuminated surface regions. With this tool, we are able to use blue light to pattern Escherichia coli biofilms with 25 μm spatial resolution. We present an accompanying biophysical model to understand the mechanism behind light-regulated biofilm formation and to provide insight on related natural biofilm processes. Overall, this biofilm patterning tool can be applied to study natural microbial communities as well as to engineer living biomaterials.
Biological regulatory systems, such as cell signaling networks, nervous systems and ecological webs, consist of complex dynamical interactions among many components. Network motif models focus on small sub-networks to provide quantitative insight into overall behavior. However, such models often overlook time delays either inherent to biological processes or associated with multi-step interactions. Here we systematically examine explicit-delay versions of the most common network motifs via delay differential equation (DDE) models, both analytically and numerically. We find many broadly applicable results, including parameter reduction versus canonical ordinary differential equation (ODE) models, analytical relations for converting between ODE and DDE models, criteria for when delays may be ignored, a complete phase space for autoregulation, universal behaviors of feedforward loops, a unified Hill-function logic framework, and conditions for oscillations and chaos. We conclude that explicit-delay modeling simplifies the phenomenology of many biological networks and may aid in discovering new functional motifs.
Lateral inhibition represents a well-studied example of biology's ability to self-organize multicellular spatial patterns with single-cell precision. Despite established biochemical mechanisms for lateral inhibition (e.g., Delta-Notch), it remains unclear how cell-cell signaling delays inherent to these mechanisms affect patterning outcomes. We investigate a compact model of lateral inhibition highlighting these delays and find, remarkably, that long delays can ensure defect-free patterning. This effect is underscored by an interplay with synchronous oscillations, cis interactions, and signaling strength. Our results suggest that signaling delays, though previously posited as a source of developmental defects, may in fact be a general regulatory knob for tuning developmental robustness.
Interacting with biological systems via experiments is important for academia, industry, and education, but access barriers exist due to training, costs, safety, logistics, and spatial separation. High-throughput equipment combined with web streaming could enable interactive biology experiments online, but no such platform currently exists. We present a cloud experimentation architecture (paralleling cloud computation), which is optimized for a class of domain-specific equipments (biotic processing units -BPU) to share and execute many experiments in parallel remotely and interactively at all time. We implemented an instance of this architecture that enables chemotactic experiments with a slime mold Physarum Polycephelum. A user study in the blended teaching and research setting of a graduate-level biophysics class demonstrated that this platform lowers the access barrier for non-biologists, enables discovery, and facilitates learning analytics. This architecture is flexible for integration with various biological specimens and equipments to facilitate scalable interactive online education,
Microbial community function depends on both taxonomic composition and spatial organization. While composition of the human gut microbiome has been deeply characterized, less is known about the organization of microbes between regions such as lumen and mucosa and the microbial genes regulating this organization. Using a defined 117 strain community for which we generate high-quality genome assemblies, we model mucosa/lumen organization with in vitro cultures incorporating mucin hydrogel carriers as surfaces for bacterial attachment. Metagenomic tracking of carrier cultures reveals increased diversity and strain-specific spatial organization, with distinct strains enriched on carriers versus liquid supernatant, mirroring mucosa/lumen enrichment in vivo. A comprehensive search for microbial genes associated with this spatial organization identifies candidates with known adhesion-related functions, as well as novel links. These findings demonstrate that carrier cultures of defined communities effectively recapitulate fundamental aspects of gut spatial organization, enabling identification of key microbial strains and genes.
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