Research stay at UC3M: DEPARTMENT OF BIOENGINEERING AND AEROSPACE ENGINEERING.
TITLE OF THE PROJECT at UC3M: Experimental and computational methodologies to measure the intercellular forces during tissue morphogenesis
In three-dimensional living tissues, cell-cell confinement, cell-cell traction forces, and the resulting intracellular tension play a key role in regulating not only cell proliferation (cell division), but more importantly, cell differentiation, cell migration, and apoptosis (programmed cell death). Yet, the molecular mechanisms that underlie the biochemical response of living cells to these mechanical forces are largely elusive. One of the reasons for this limited understanding has been the lack of suitable methods to measure accurately the intercellular forces in three-dimensional, developing living tissues with high spatial and temporal resolution. Thus, the main objective of this research project is to develop novel experimental and computational methodologies to measure the spatial and temporal evolution of the intercellular forces during three-dimensional tissue development. Our basic idea is to place small diameter, slender, deformable PDMS microrods in a developing tissue and to measure their shape deformations due to the forces exerted by the cells. This methodology will be tested and optimized using sophisticated 3D organotypic skin cultures containing keratinocytes producing GFP (Green Fluorescence Protein) and monitored by confocal microscopy. The project required a multidisciplinary approach and will be conducted by a team of senior investigators, with long-term experience in tissue engineering, skin biology and pathology, microfabrication, solid mechanics, mathematical modeling, and computational techniques. Our proposal is transformative from a scientific point of view and in the long term will lead to a better knowledge of the pathogenesis of diseases and open the door to improved diagnostics and treatments.
Stay period: MAR 14 - JUN 15