Assembly & Curvature Sensing of Septin Cytoskeletal Proteins
This research direction is done in collaboration with the Gladfelter Lab, and it’s all centered around the least explored (but equally fascinating) member of cytoskeletal filaments called Septin! they are labeled with green color in the image. The number of papers published on septin is almost 100 times less than actins and microtubules! One amazing property of septin is that it can sense and localize to sites of positive micron-scale membrane curvature in Eukaryotic cells from yeast to humans. But, the underlying physical principles that control this process remain poorly understood.
In collaborative with the Gladfelter Lab, we used a combination of kinetic modeling, SEM and quantitative microscopy and found that curvature sensing emerges from the integration of multiple different steps of assembly at different lengthscales and timescales rather than being a simple one component process. This means that the cell shape is being sensed through the control of timing of multiple binding and assembly steps between septins oligomers and the membrane rather than simply matching the geometry of the molecules.
We are now working on developing a multiscale mechanical model of septin assembly and curvature sensing that is guided and tested by experiments.
Related Publications:
Edelmaier, C. J., Klawa, S. J., Mofidi, S. M., Wang, Q., Bhonge, S., Vogt, E. J., ... & Nazockdast, E. (2024). Charge distribution and helical content tune the binding of septin’s amphipathic helix domain to lipid membranes. bioRxiv, 2024-07.
Shi, W., Cannon, K. S., Curtis, B. N., Edelmaier, C., Gladfelter, A. S., & Nazockdast, E. (2023). Curvature sensing as an emergent property of multiscale assembly of septins. Proceedings of the National Academy of Sciences, 120(6), e2208253120.
