Collaborative Research NSF-ANR: Mechanisms of terminal erythroid enucleation

a. Objectives and research hypothesis a1. Objectives The RedEnuc project aims to decipher the physical mechanisms at play in enucleation during mammalian erythropoiesis: the process red blood cells (RBCs) are generated. Our general objective is to elucidate the role of the mechanical constraints exerted on the erythroblasts / nascent reticulocytes on the extrusion and detachment of nuclei. Our specific objectives are: 1. To develop an in vitro approach to quantitatively measure the physical forces experienced by erythroblasts and nascent reticulocytes, 2. To highlight the role of the forces experienced in a crowded environment and triggered mechanosensitive response in the cells on nuclear extrusion, 3. To elucidate how external squeezing and shearing forces contribute to nucleus detachment, 4. To develop a multiscale computational model to predict the acto-myosin generated internal active force that drives nucleus extrusion and its dependence on mechanosensing, and to predict the external squeezing and shearing forces that promote nucleus detachment.