Self-organization in bacterial systems results from the interplay between physical and biological interactions. The project aims at identifying these interactions and understanding the complex interplay between them in various observed collective patterns of bacteria.
We propose a novel approach to study bacterial multicellular organization based on physical mechanisms in order to identify the minimum elements of biochemical regulation required to coordinate complex processes such as bacterial clustering, stream formation, and fruiting body formation. This is a multidisciplinary project involving mathematical modeling, large-scale simulations, and biological experiments. It aims at: i) the development of realistic microscopic models for pattern formation in bacteria, and ii) the derivation of the corresponding hydrodynamic equations to describe the macroscopic behavior of a bacterial colony/biofilm. This is an ambitious plan that involves developing new physics and mathematics, together with a strong experimental component. The development of such theoretical framework will have an impact way beyond bacterial modeling and can be placed in the broader focus of active matter theory, which has applications as diverse as in tissue growth and in the engineering of biomimetic materials.
The idea is to use simple experiments with bacteria, using phase contract microscopy to record their position and orientation over time. Analyze these data to build agent-based models (ABM) consistent with experimental observation at the individual level. The next step is to analyze the large-scale properties of the ABM via large-scale simulations and compare these results with the experimental observation at the colony level. Finally, the intention is to coarse-grain the ABM to arrive to a description in term of hydrodynamic equations and understand the emerging pattern in terms of these equation. This will allow us to classify collective behaviors and identify the essential microscopic ingredients, as well as to place studied bacterial patterns in the broader context of active matter.
Work and progress has been made at the level of:
a) Theory, which includes large-scale simulations and derivation of hydrodynamic equations
b) Experiments, data analysis, and mathematical modeling, which include experiments with bacteria, image analysis, tracking algorithms, simulations, and analytical calculations.
The results obtained so far have exceeded the initial expectations, and some of the published results triggered the interest of the scientific media. Below, we list some of the scientific results obtained:
- We found that it is possible to describe the regulation of velocity reversals observed in some bacteria such as myxobacteria using an internal clock. By coupling this clock model with a motility model we discover non-trivial transport properties and the existence of an optimal noise.
- We found there exist instabilities that lead to the formation high density-regions where bacteria accumulate and move nematically (called bands) in the absence of biochemical communication and only due to physical interactions.
- We showed that short-range attractive interactions, if Newton’s third law is broken, can lead to a plethora of self-organized patterns including nematic band and vortex formation as observed in some bacterial systems.
- Using experiments with Salmonella swimming close to the surface, where host cells were anchored, we showed search process for host cells is mainly stochastic, chemotaxis does not operate, and the inter-individual variability of diffusion coefficients ranges over four orders of magnitude.
A series of new interdisciplinary works, combining experiments and theory are expected for the second part of the project, as well as new theoretical works.
The initial obtained results allowed us to conceive two new projects, one focused on alternative strategies to fight against bacterial infections in collaboration with D. Czerucka, external collaborator in this project (with F. Peruani as PI), and a second one, focused on the multi-scales associated with the myxobacterial life cycle in collaboration with the experimental group of Tam Mignot in Marseille.
1. Diffusion properties of active particles with directional reversal, R. Grossmann, F. Peruani, M. Bär, New J. Phys. 18 043009 (2016)
[Read a Perspective on this work by Carsten Beta : iopscience.iop.org/article/10.1088/1367-2630/18/5/051003/meta]
2. Pattern formation of self-propelled rods with directional reversal, R. Grossmann, F. Peruani, M. Bär, Phys. Rev. E 93, 040102(R) (2016)
3. Large-scale patterns in a minimal cognitive flocking model: incidental leaders, nematic patterns, and aggregates, L. Barberis, F. Peruani, Phys. Rev. Lett. 117, 248001 (2016)
[Read the Synopsis: «Flocks Without Memory« by Matteo Rini in Physics: physics.aps.org/synopsis-for/10.1103/PhysRevLett.117.248001 -- the article was covered in other news outlets as well]
4. Hydrodynamic equations for flocking models without velocity alignment, F. Peruani, J. Phys. Soc. Jpn. 86, 101010 (2017)
5. Salmonella Typhimirium in the search of host cells, S. Otte, E. Perez-Ipiña, R. Pointier-Bres, D. Czerucka, F. Peruani, Submitted 2017
6. A polar bundle of flagella can drive bacterial swimming by pushing, pulling, or coiling around the cell body, M. Hintsche, V. Waljor, R. Grossmann, Marco J. Kuhn, K.M. Thormann, F. Peruani, C. Beta, submitted (2017)
Bacterial survival is a collective phenomenon for the great majority of bacterial species that requires multicellular organization. This is the case, for instance, for myxobacteria that exhibit a very complex multicellular behavior and are used as model organisms to study bacterial pattern formation processes such as: aggregation, collective adaptation, cell differentiation, collective swarming, and the morphologically complex fruiting body formation. Understanding multicellular organization in bacteria is fundamental to get an insight into important processes such as bacterial infections and the bacterial regulated nitrogen, carbon, and sulfur cycles required to sustain life in soils, waters, and atmosphere. In short, life on earth, in its present form, is highly dependent on bacterial survival, and bacteria are key to control our environment.
We propose a novel approach to study bacterial multicellular organization based on physical mechanisms in order to identify the minimum elements of biochemical regulation required to coordinate complex processes such as fruiting body formation. This is a multidisciplinary project involving mathematical modeling, large-scale simulations, and biological experiments. It aims at: i) the development of realistic microscopic models for pattern formation in myxobacteria, and ii) the derivation of the corresponding hydrodynamic equations to describe the macroscopic behavior of the colony. This is an ambitious plan that involves developing new physics and mathematics, and performing some fundamental experiments with bacteria. The development of such theoretical framework will have an impact way beyond bacterial modeling and the understanding of bacterial pattern formation and can be placed in the broader focus of active matter theory, which has applications as diverse as in tissue growth and in the engineering of biomimetic materials.
Monsieur Fernando Peruani (UNIVERSITE NICE SOPHIA ANTIPOLIS Laboratoire Jean Alexandre Dieudonné)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
UNS/LJAD UNIVERSITE NICE SOPHIA ANTIPOLIS Laboratoire Jean Alexandre Dieudonné
Help of the ANR 198,178 euros
Beginning and duration of the scientific project: September 2015 - 36 Months