Children are said to be a product of both nature and nurture – of their genes and the environment in which they are raised. The cells of the growing liver are not so different in this sense. As the liver of a fetus develops, immature cells called liver progenitors mature to become one of two types of adult cells: the hepatocytes that form the bulk of the liver, or the biliary cells that make up the bile duct. The traditional view is that genetic factors mainly control which cell type the progenitor cells become. However, recent research suggests that the environment around the cells matters more in this process than once thought. Cells can respond to the physical properties of their environment, such as the structure and stiffness of the surrounding tissue. These properties change as the liver develops, and can also be altered by disease. For example, damaged liver cells can spit out proteins that harden and form stiff scars. This raises a question: do changes in stiffness affect how progenitor cells behave? To answer this question, Kaylan et al. printed collagen in circular patterns and grew liver progenitor cells on them. The cells at the edges of the circular patterns matured into bile duct cells, while those in the center became hepatocytes. The stiffness felt by the cells was then determined by measuring the level of mechanical stress that they experienced. This revealed that the cells at the edge of the collagen pattern – the cells that became bile duct cells – were under most stress. In addition, more bile duct cells formed when progenitor cells were grown on a stiffer collagen pattern. Overall, the results reported by Kaylan et al. suggest that the stiffness of the environment, and the resulting stresses on a progenitor cell, can influence how it matures. As well as helping us to understand how the liver develops, this knowledge could also help us to treat a group of diseases called cholangiopathies, in which the bile ducts become inflamed. These diseases are thought to be caused by certain cells (which are similar to liver progenitor cells) maturing to become incorrect cell types. Future studies could determine if preventing changes in stiffness in the environment of these cells, or slowing their response to such changes, would help patients.
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Mechanical instability and interfacial energy drive biofilm morphogenesis
Engineers have long studied how mechanical instabilities cause patterns to form in inanimate materials, and recently more attention has been given to how such forces affect biological systems. For example, stresses can build up within a tissue if one layer grows faster than an adjacent layer. The tissue can release this stress by wrinkling, folding or creasing. Though ancient and single-celled, bacteria can also develop spectacular patterns when they exist in the lifestyle known as a biofilm: a community of cells adhered to a surface. But do mechanical instabilities drive the patterns seen in biofilms? To investigate, Yan, Fei, Mao et al. grew biofilms of the bacterium called Vibrio cholerae – which causes the disease cholera – on solid, non-growing ‘substrates’. This work revealed that as the biofilms grow, their expansion is constrained by the substrate, and this situation generates mechanical stresses. To release the stresses, the biofilm initially folds to form wrinkles. Later, as the biofilm expands further, small parts of it detach from the substrate to form blisters. The same forces that keep water droplets spherical (known as interfacial forces) dictate how the blisters evolve, interact, and eventually shape the expanding biofilm. Using these principles, Yan et al. could engineer the biofilm into desired shapes. Collectively, the results presented by Yan et al. connect the shape of the biofilm surface with its material properties, in particular its stiffness. Understanding this relationship could help researchers to develop new ways to remove harmful biofilms, such as those that cause disease or that damage underwater structures. The stiffness of biofilms is already known to affect how well bacteria can resist antibiotics. Future studies could look for new genes or compounds that change the material properties of a biofilm, thereby altering the biofilm surface.
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- NSF-PAR ID:
- 10093752
- Date Published:
- Journal Name:
- eLife
- Volume:
- 8
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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During development, organisms acquire three-dimensional (3D) shapes with important physiological consequences. While basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developing
Vibrio cholerae biofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat but later undergo a mechanical instability and become wrinkled. To gain mechanistic insights into this dynamic pattern-formation process, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the substrate, and the friction between them. Our model shows quantitative agreement with experimental measurements of biofilm expansion dynamics, and it accurately predicts two distinct spatiotemporal patterns observed in the experiments—the wrinkles initially appear either in the peripheral region and propagate inward (soft substrate/low friction) or in the central region and propagate outward (stiff substrate/high friction). Our results, which establish that nonuniform growth and friction are fundamental determinants of stress anisotropy and hence biofilm morphology, are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns. We discuss the implications of forming undulated biofilm morphologies, which may enhance the availability of nutrients and signaling molecules and serve as a “bet hedging” strategy. -
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Abstract The ability of bacteria to colonize and grow on different surfaces is an essential process for biofilm development. Here, we report the use of synthetic hydrogels with tunable stiffness and porosity to assess physical effects of the substrate on biofilm development. Using time-lapse microscopy to track the growth of expanding Serratia marcescens colonies, we find that biofilm colony growth can increase with increasing substrate stiffness, unlike what is found on traditional agar substrates. Using traction force microscopy-based techniques, we find that biofilms exert transient stresses correlated over length scales much larger than a single bacterium, and that the magnitude of these forces also increases with increasing substrate stiffness. Our results are consistent with a model of biofilm development in which the interplay between osmotic pressure arising from the biofilm and the poroelastic response of the underlying substrate controls biofilm growth and morphology.
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Abstract Microorganisms navigate and divide on surfaces to form multicellular structures called biofilms, the most widespread survival strategy found in the bacterial world. One common assumption is that cellular components guide the spatial architecture and arrangement of multiple species in a biofilm. However, bacteria must contend with mechanical forces generated through contact with surfaces and under fluid flow, whose contributions to colonization patterns are poorly understood. Here, we show how the balance between motility and flow promotes the emergence of morphological patterns in
Caulobacter crescentus biofilms. By modeling transport of single cells by flow and Brownian-like swimming, we show that the emergence of these patterns is guided by an effective Péclet number. By analogy with transport phenomena we show that, counter-intuitively, fluid flow represses mixing of distinct clonal lineages, thereby affecting the interaction landscapes between biofilm-dwelling bacteria. This demonstrates that hydrodynamics influence species interaction and evolution within surface-associated communities. -
Bacteria in porous media, such as soils, aquifers, and filters, often form surface-attached communities known as biofilms. Biofilms are affected by fluid flow through the porous medium, for example, for nutrient supply, and they, in turn, affect the flow. A striking example of this interplay is the strong intermittency in flow that can occur when biofilms nearly clog the porous medium. Intermittency manifests itself as the rapid opening and slow closing of individual preferential flow paths (PFPs) through the biofilm–porous medium structure, leading to continual spatiotemporal rearrangement. The drastic changes to the flow and mass transport induced by intermittency can affect the functioning and efficiency of natural and industrial systems. Yet, the mechanistic origin of intermittency remains unexplained. Here, we show that the mechanism driving PFP intermittency is the competition between microbial growth and shear stress. We combined microfluidic experiments quantifying Bacillus subtilis biofilm formation and behavior in synthetic porous media for different pore sizes and flow rates with a mathematical model accounting for flow through the biofilm and biofilm poroelasticity to reveal the underlying mechanisms. We show that the closing of PFPs is driven by microbial growth, controlled by nutrient mass flow. Opposing this, we find that the opening of PFPs is driven by flow-induced shear stress, which increases as a PFP becomes narrower due to microbial growth, causing biofilm compression and rupture. Our results demonstrate that microbial growth and its competition with shear stresses can lead to strong temporal variability in flow and transport conditions in bioclogged porous media.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.7554/eLife.43920
