Giel Vankevelaer

Mechanobiology is the interdisciplinary study of how mechanical forces influence the structure, function, and behavior of living cells and tissues. A key focus in this field is the mechanotransduction, where cells sense and respond to forces from their environment. Focal adhesions are the major structural elements of the mechanotransduction, acting as molecular machinery connecting the cell to its surroundings and transmitting the forces in both directions. Understanding the mechanical forces over focal adhesions is crucial for unraveling how cells behave in different environments and contribute to the overall function of tissues and development of pathological conditions. During this interdisciplinary project, the student will combine a variety of top-notch techniques. Optogenetics is a technique that involves the use of genetically encoded light-sensitive proteins to control and manipulate cellular processes with high precision, enabling the targeted activation or inhibition of certain signaling pathways. In this study, the student will use recently developed optogenetics tool to regulate the cellular contractility. Consequent change of contractility will be correlated with the changes of molecular forces in focal adhesions by using two recently developed tools; FRET-based Molecular Tension Probes and DNA Force Sensors. This will allow the investigation both intracellular and extracellular forces on single-molecule level. To obtain a visual output of the cellular forces, the student will learn how to work with Fluorescence Lifetime Imaging Microscopy, an advanced fluorescence microscopy technique that allows users to obtain FRET efficiency with high precision based on molecular lifetime information. If the time allows, the student will investigate the cellular forces in 3D cell culture models, using a biomimetic synthetic hydrogel to change the architectural (i.e. porosity) and mechanical (i.e. stiffness) biochemical (i.e. the adhesion ligand) properties of the extracellular matrix (ECM). At the end of this project, the student will therefore acquire expertise in molecular cloning, optogenetics, FRET-based tension probes, DNA nanotechnology, advanced microscopy and 3D hydrogel-based cell culture models.