Til bevillingsoversigt

Understanding and regulating membrane tension for the nano-bio interface

Carlsberg Foundation 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.

SSR

Scientific progress has led to an improved understanding of cell physiology, which in turn has led to a better understanding of many human diseases and the development of therapeutic drugs. Our understanding of membrane tension regulation is still limited, but the importance of tension in many cellular processes has already been established. An improvement of the biophysical model of membrane tension consequently holds promise not only for our fundamental understanding of cell physiology, but also for the future discovery and use of therapeutic drugs.