NSF-ANR MCB/PHY: The Emergence of Long-Range Coherence in Motile Microorganismal Systems with Quenched Disorder

Self-propelled motion leading to large-scale collective behavior occurs in living and synthetic systems across scales. Controlling the emergent collective behavior of cells and bacteria is a key step toward the design of living and biomimetic materials and advancing 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. The consensus in the active matter community is that in ensembles of microorganisms, the emergent order originates from local aligning interaction between neighbors and the misaligning 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. The goal of this award is to combine experiments and predictive theoretical modeling to conceive synthetic environments in which the microorganisms -- bacteria, amoeba, and mammal cells -- exhibit a controlled collective behavior and execute a desired function. 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) bacteria and amoeba 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 demonstrate surface motility and chemotaxis. The research will enable the controlling of living active matter with long-range hydrodynamic interactions (bacteria) and short-range steric interactions (cells). The primary outcome of this award will be the fundamental insights into the motility of bacterial and eukaryotic cells in a heterogeneous environment closely resembling realistic conditions. It will benefit the broad scientific community by better understanding cell migration, which is crucial in the context of bacterial infections and cancer cell invasion. The research will also stimulate experimental techniques and predictive mathematical tools for new biological materials and innovative biomedical technologies. A unique aspect of the award is the organization of the French-American school “Living Disordered Active Matter.” Through research and organization of the school, participating students and postdocs will benefit from interdisciplinary training and education. They will be exposed to advanced methods in the physics of biological systems, applied mathematics, computations, and experimental techniques. This collaborative US/France project is supported by the Physics of Living Systems program in the Division of Physics at the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.