Understanding and regulating membrane tension for the nano-bio interface
Name of applicant
Lasse Hyldgaard Klausen
Institution
Aarhus University
Amount
DKK 1,190,099
Year
2019
Type of grant
Reintegration Fellowships
What?
The cell membrane surrounds all living cells, protecting them from the environment and taking care of the transport of nutrients in and wastes out. Similar to a balloon, the cell is inflated and the membrane is always under pressure. But this tension is constantly changing, and recently it was discovered that tension can even fluctuate from one part of the cell to another. How the cell regulates and uses the spatial membrane tension is largely unknown. This project is aimed at improving the biophysical model of membrane tension, exploring how tension is affected by external stimuli and investigating the molecular mechanisms employed by the cell in order to regulate tension.
Why?
Membrane tension directly regulates many cell behaviours, such as vesicle trafficking and cell motility, while simultaneously working as a sensing mechanism for the cell. For example during sudden changes in the osmolarity of blood, where membrane tension regulation initiates a rapid mechanoprotective mechanism. Deficiencies in cellular response mechanisms to tension can be detrimental and have been strongly associated to cancer development. While the importance of membrane tension has been broadly recognized, a new model of membrane tension regulation is necessary. This will lead to a better understanding of membrane tension related diseases and could be essential for the development of treatments.
How?
Single-molecule force spectroscopy will be used to simultaneously measure local membrane tension and cytoskeletal stiffness of human vascular endothelial cells under osmotic shock, as a model system for studying the effects of blood thinning on the cardiovascular system. This work will be accompanied by an in vitro study of artificial lipid bilayers tethered to nanofabricated substrates for a better understanding of the propagation of membrane tension.