David and Goliath at the cell surface: Photo-crosslinkable lipid derivatives to control membrane mechanics

We propose to develop state-of-the-art lipid derivatives to modulate membrane viscosity, finally offering researchers a comprehensive toolbox to unlock the importance of this understudied cellular parameter. It is known that cells regulate membrane viscosity by changing the lipid composition of the membrane. We will develop and characterize caged lipid derivatives which can be loaded into the cell, stored in endomembranes (i.e. the Golgi and ER) and then uncaged by light to be released to the plasma membrane in a controlled and scalable manner. Our toolbox will include photocrosslinkable lipid derivatives, allowing for precise control of membrane biophysics, and enabling the targeted formation of lipid islands. Finally, as a proof of principle, we will apply these tools to reveal the role of membrane viscosity in cell form and function. 

• Manipulation of the plasma membrane lipid composition by uncaging lipid derivatives. 

• Manipulation of the plasma membrane biophysics by photo-crosslinkable lipids 

• How does altered viscosity affect cell form and function 

This project is part of the 2024 Membrane Biophysics cohort

Researchers in this cohort will focus on cellular membranes that separate cell contents from the surrounding environment, allow cells to change shape, exchange materials, and respond to their environment. Despite having been implicated in numerous human diseases, little is known about the principles governing cell membrane biology and biophysics. This cohort will expand the frontiers of our understanding of fundamental aspects of cell membrane form, function, and dynamics using innovative technologies and analytical frameworks, with important implications for basic science and human health.