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How neurons sense tissue stiffness during maturation
Secondary Supervisor(s): Dr Darius Koester
University of Registration: University of Warwick
BBSRC Research Themes:
Project Outline
For decades, neuroscience has primarily focused on chemical signalling. More recently, however, it has become clear that mechanical cues - such as the stiffness of surrounding tissue - also play a crucial role in neuronal development. Our previous work shows that neuronal maturation depends strongly on local mechanical properties: neurons mature earlier in softer brain regions and more slowly in stiffer ones. What remains unknown is how neurons detect these differences in stiffness.
Neurons engage with their environment through the cell membrane, adhesion sites, and the cytoskeleton, actively pulling on their surroundings to probe mechanical properties. This mechanosensitive interface is essential for detecting stiffness and translating it into developmental changes. This project will investigate how these interactions shape neuronal maturation.
The student will use calcium imaging and immunofluorescence to study how rat neurons develop in vitro on substrates of different stiffnesses. CRISPR-Cas9 gene editing will be used to knock down candidate proteins for stiffness sensing. The cell-substrate interface will be studied using surface plasmon resonance microscopy. In collaboration with the Koester lab the cytoskeletal organisation and membrane properties will be measured using fluorescence microscopy and optical tweezers.
Together, this will clarify how mechanical input is coupled to membrane and cytoskeletal dynamics, and ultimately to neuronal maturation. This work will advance our understanding of how neurons sense and respond to their physical environment during development.