Laurens Kimps

Combining molecular sensors and high-resolution imaging for quantifying sub-cellular forces
Started on October, 2020

email Laurens Kimps

Mechanical forces play a critical role during the evolution of the most important biological processes, such as the formation of new blood vessels or embryonic development. Cellular and tissue-level forces direct cell migration, drive tissue morphogenesis and regulate organ growth. Despite the relevance of mechanics for these processes, our knowledge of the dynamics of mechanical forces in living tissues remains scarce. In the last years, high resolution three-dimensional traction force microscopy (TFM) has been developed to unveil the underlying mechanical forces during cell migration and invasion in in-vitro environments. However, the resolution of this technique still remains at cellular level. To address this problem, recent studies have developed tension sensors based on Förster Resonance Energy Transfer (FRET). These sensors are integrated into force bearing proteins and allow the measurement of mechanical tensions on subcellular structures, like nuclear proteins. The aim of this project is to measure subcellular forces in particular at cell adhesion sites, by means of a FRET-Vinculin tension sensor and at the same time correlate with measurements performed by means of TFM techniques. The student will work with cell culture systems in particular with endothelial cells and will introduce the FRET-tension sensors within the cells by transfection technologies. At the same time the student will work with 3-D reconstituted hydrogels, mainly with Polyacrylamide gels, in order to mimic the real cellular forces exerted in the surrounding extracellular matrix. Finally, the student will image the expression of the sensors by using confocal microscopy imaging and will apply imaging techniques to process the acquired data. We are looking for a creative and motivated student interested in cell biology & tissue engineering, biomechanics and image processing