Description du projet
La mesure de la force nanoscopique révèle la manière dont les bactéries «fléchissent leurs muscles»
Outre la signalisation chimique et électrique, les micro-organismes et les cellules utilisent des entrées et des sorties mécaniques pour exécuter leurs fonctions essentielles. En réponse à des signaux chimiomécaniques, les bactéries génèrent des forces de traction essentielles pour leur permettre de coloniser les surfaces, créer des biofilms et envahir des cellules hôtes. Toutefois, les voies transduisant les entrées en sorties, et même les entrées et les sorties elles-mêmes, sont mal comprises, en grande partie du fait de la difficulté à mesurer ces forces infimes chez des bactéries qui se déplacent librement. Le projet BacForce, financé par l’UE, met au point des méthodes pionnières pour observer ces forces. Des techniques expérimentales combinées à des simulations informatiques permettront aux scientifiques de manipuler et de caractériser la génération de forces de traction bactérienne, fournissant ainsi d’importantes informations sur la formation de biofilms et une application de grande envergure pour la génération de forces nanoscopiques à partir de cellules.
Objectif
Bacteria can generate mechanical forces that are important for the colonization of surfaces, formation of biofilms, and infection of host cells. This proposal addresses the fundamental question of how bacteria can control their force generation to robustly respond to chemo-mechanical cues on complex surfaces. Currently, a knowledge gap exists between the molecular regulation pathways on the one hand and the mechanical behavior on the other hand. One major impediment for understanding of how behavior is connected to control is, to date, the impossibility of studying bacterial force directly in unconstrained situations. Based on an initial study, I propose employing new methods for the unperturbed, high-resolution measurement of bacterial traction forces on wide spatiotemporal scales. Thus, the force-generation linking behavior to control can be investigated directly.
The objectives are to (A) gain access to nanoscopic mechanical phenomena through the development of cutting-edge super-resolution traction force microscopy, (B) employ the methods to characterize how Pseudomonas aeruginosa controls pilus-generated forces while responding to chemical cues, and (C) establish how surface rigidity affects force generation by P. aeruginosa during biofilm formation. In an interdisciplinary approach, I will combine traction measurements with genetic perturbations, molecule labeling, and computer simulations to produce functional models of the mechanocontrol strategies.
Altogether, I will establish a novel technique, opening up the possibility of studying nanoscopic force generation in many types of cells. Through these advances, I will characterize a set of mechanoregulation strategies in P. aeruginosa that are paradigmatic for diverse Gram-negative pathogens employing the same type of pili. Broadly, I expect that the studied bacterial control strategies have a generic, minimal nature and can appear as basic motives throughout development, homeostasis, and disease.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
80539 MUNCHEN
Allemagne