skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Cell dispersal by localized degradation of a chemoattractant
Significance Many studies have investigated how cells can move toward the source of a chemoattractant, but relatively little is known about mechanisms that can cause cells to move away from a location. Here, we show that small aggregates of the social amoebaDictyostelium discoideumcan show dispersal behavior during which cells are moving away from the aggregate. Using a combination of experiments and modeling, we show that this dispersal can arise due to a competition between the diffusible chemoattractant and the enzyme that degrades it, and that the localized degradation of the chemoattractant may be a mechanism for morphogenesis.  more » « less
Award ID(s):
1707637
PAR ID:
10212401
Author(s) / Creator(s):
 ;  ;  ;  
Publisher / Repository:
Proceedings of the National Academy of Sciences
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
118
Issue:
6
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; (, mSystems)
    Rodríguez-Verdugo, Alejandra (Ed.)
    ABSTRACT The soil bacteriumMyxococcus xanthusis a model organism with a set of diverse behaviors. These behaviors include the starvation-induced multicellular development program, in which cells move collectively to assemble multicellular aggregates. After initial aggregates have formed, some will disperse, with smaller aggregates having a higher chance of dispersal. Initial aggregation is driven by two changes in cell behavior: cells slow down inside of aggregates and bias their motion by reversing direction less frequently when moving toward aggregates. However, the cell behaviors that drive dispersal are unknown. Here, we use fluorescent microscopy to quantify changes in cell behavior after initial aggregates have formed. We observe that after initial aggregate formation, cells adjust the bias in reversal timings by initiating reversals more rapidly when approaching unstable aggregates. Using agent-based modeling, we then show dispersal is predominantly generated by this change in bias, which is strong enough to overcome slowdown inside aggregates. Notably, the change in reversal bias is correlated with the nearest aggregate size, connecting cellular activity to previously observed correlations between aggregate size and fate. To determine if this connection is consistent across strains, we analyze a secondM. xanthusstrain with reduced levels of dispersal. We find that far fewer cells near smaller aggregates modified their bias. This implies that aggregate dispersal is under genetic control, providing a foundation for further investigations into the role it plays in the life cycle ofM. xanthus. IMPORTANCEUnderstanding the processes behind bacterial biofilm formation, maintenance, and dispersal is essential for addressing their effects on health and ecology. Within these multicellular communities, various cues can trigger differentiation into distinct cell types, allowing cells to adapt to their specific local environment. The soil bacteriumMyxococcus xanthusforms biofilms in response to starvation, marked by cells aggregating into mounds. Some aggregates persist as spore-filled fruiting bodies, while others disperse after initial formation for unknown reasons. Here, we use a combination of cell tracking analysis and computational simulations to identify behaviors at the cellular level that contribute to aggregate dispersal. Our results suggest that cells in aggregates actively determine whether to disperse or persist and undergo a transition to sporulation based on a self-produced cue related to the aggregate size. Identifying these cues is an important step in understanding and potentially manipulating bacterial cell-fate decisions. 
    more » « less
  2. ; ; (, AIChE Journal)
    Abstract When chemotactic bacteria are exposed to a concentration gradient of chemoattractant while flowing along a channel, the bacteria accumulate at the interface between the chemoattractant source and bacterial suspension. Assuming that the interface is no‐slip, we can apply the shear flow approximation near the no‐slip boundary and solve a steady‐state convection‐diffusion model for both chemoattractant and bacterial concentrations. We suggest similarity solutions for the two‐dimensional problem and identify a critical length scaleηcfor bacteria chemotaxis in a given concentration gradient. The analysis identifies three dimensionless groups representing, respectively, chemotactic sensitivity, the chemotaxis receptor constant, and the bacteria diffusion coefficient, which typically show coupled effects in experimental systems. We study the effect of the dimensionless groups separately and provide understanding of the system involving shear flow and chemotaxis. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al (, Science)
    Moving cells can sense and respond to physical features of the microenvironment; however, in vivo, the significance of tissue topography is mostly unknown. Here, we usedDrosophilaborder cells, an established model for in vivo cell migration, to study how chemical and physical information influences path selection. Although chemical cues were thought to be sufficient, live imaging, genetics, modeling, and simulations show that microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated near the center of the egg chamber. E-cadherin supplies a permissive haptotactic cue. Our results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path among many. 
    more » « less
  4. ; ; ; (, iScience)
    Cell migration is critical throughout a multicellular organism’s life from embryogenesis to immune response and tissue repair and can even go aberrantly wrong in diseases like metastatic cancer. In vitro, graded concentrations of diffusible chemoattractants can guide migrating cells, but less is known about chemoattractant distribution and chemotaxis within living organisms, which have complex tissue geometries. Using the border cells, which migrate collectively in the Drosophila egg chamber during oogenesis, we studied how tissue structure affects chemotaxis in vivo. Live-imaged border cells exhibited variations in their chemotactic migration, which correlated positionally within distinct tissue architectures, specifically acellular gaps at cell-cell intersections. To determine how different regions in the egg chamber’s geometry affect chemical cues, we developed a partial differential equation (PDE) model of chemoattractant distribution within a relevant in silico domain. Using a hybrid mathematical model that couples the chemoattractant PDE and an agent-based motion of the cluster, we found that larger extracellular volumes within intersections could locally dampen chemoattractant gradient magnitudes and slow cluster speed in simulations. In vivo, in response to genetically increasing the levels of a chemoattractant, PDGF- and VEGF-related factor 1, border cells exhibited delayed migration and behaved differently within specific architectural regions, consistent with results in silico. We next altered the architectural regions in the migration domain in half pint (hfp) mutant egg chambers and observed migration behaviors that still correlated with tissue features. Importantly, the abnormal tissue geometry was sufficient to rescue defects due to high levels of chemoattractant and resulted in punctual border cell migration indicating chemoattractant distribution can depend on tissue structure. Our modeling data indicate that chemoattractants are more concentrated in certain tissue architectures and dispersed in other regions, likely informing cell migration speeds and favoring clustered cell movements in tissue that contain varied architectures in vivo. Our results shed light on the intricate interplay between tissue geometry and the local distribution of important signaling molecules in orchestrating the essential process of cell migration. 
    more » « less
  5. ; ; ; ; ; ; ; (, Movement Ecology)
    Abstract PurposeTrailing-edge populations at the low-latitude, receding edge of a shifting range face high extinction risk from climate change unless they are able to track optimal environmental conditions through dispersal. MethodsWe fit dispersal models to the locations of 3165 individually-marked black-throated blue warblers (Setophaga caerulescens) in the southern Appalachian Mountains in North Carolina, USA from 2002 to 2023. Black-throated blue warbler breeding abundance in this population has remained relatively stable at colder and wetter areas at higher elevations but has declined at warmer and drier areas at lower elevations. ResultsMedian dispersal distance of young warblers was 917 m (range 23–3200 m), and dispersal tended to be directed away from warm and dry locations. In contrast, adults exhibited strong site fidelity between breeding seasons and rarely dispersed more than 100 m (range 10–1300 m). Consequently, adult dispersal kernels were much more compact and symmetric than natal dispersal kernels, suggesting adult dispersal is unlikely a driving force of declines in this population. ConclusionOur findings suggest that directional natal dispersal may mitigate fitness costs for trailing-edge populations by allowing individuals to track changing climate and avoid warming conditions at warm-edge range boundaries. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email