NSF-ANR MCB/PHY: The emergence of long-range coherence in motile microorganismal systems with quenched disorder – MotDis

Overview
Self-propelled motion leading to large-scale collective behavior occurs in living and synthetic systems across scales. Controlling emergent collective behavior of cells and bacteria is a key step towards the design of living and biomimetic materials, including innovative biomedical technologies such as tissue engineering. Pre-patterned environments (i.e. quenched disorder) can be used to control active living systems. Still, the understanding of the effect of quenched disorder in active systems remains in its infancy. A two-prong strategy will be executed to tackle living active matter with the quenched disorder: (1) Experimental study of bacteria Bacillus subtilis, amoeba Dictyostelium discoideum, and bladder cancer cells in disordered environments; (2) Theoretical analysis of fundamental active matter models on disordered substrates. The experimental systems are chosen for the following reasons: (i) they are model microorganisms in biological research. Their behavior and genome are well- characterized. (ii) They are robust and can be grown in large quantities. (iii) Bacillus subtilis exhibit swimming motility. Dictyostelium discoideum and cancer cells demonstrates surface motility and chemotaxis. The research will enable controlling living active matter with long-range hydrodynamic interactions (bacteria) and short-range steric interaction (cells). Aronson (PI) will conduct the experimental studies. Peruani (non-NSF- funded collaborator) will focus on the computational modeling.

Intellectual Merit
The consensus in the active matter community is that in ensembles of microorganisms, the emergent order originates from aligning interaction between neighbors and the misalignment effect of the external noise, e.g., due to thermal fluctuations or bacterial run- and-tumble motion. However, external noise is not the only and, more importantly, the foremost source of misalignment. Self-propelled particles moving on a disordered substrate - bacteria swimming in a porous environment or cancer cells crawling through heterogeneous extracellular matrix - are affected by the imperfections, roughness, and random obstacles of the medium. Our goal is to combine experiments and predictive theoretical modeling to conceive environments in which the microorganisms -- bacteria, amoeba, and mammal cells -- exhibit a controlled collective behavior and execute a desired function. The PIs will develop new experimental techniques and predictive computational tools for control of motile cells in a heterogeneous environment.

Broader Impact
A fundamental understanding of the motility of bacterial and eukaryotic cells in a heterogeneous environment is crucial in the context of bacterial infections and cancer cell invasion. This research will stimulate experimental techniques and predictive mathematical tools for new biological materials and innovative biomedical technologies. The produced computational algorithms will be open-source and available to broad scientific and engineering communities. A unique aspect of the proposal is the French- American school “Living Disordered Active Matter”. Through research and organization of the school, students and postdocs will benefit from the interdisciplinary training and education. Students will learn theoretical methods in applied mathematics, computations, and experimental techniques employed in biological physics and engineering.