Project description
Insight into the mechanics and interactions of cytoskeletal elements
Cytoskeletal filaments are dynamic structures that provide shape, support and organisation to cells. They consist of three main types: microfilaments, intermediate filaments (IFs) and microtubules, each playing distinct roles in cell movement, division and intracellular transport. IFs, particularly vimentin, are less studied despite their emerging role in epithelial cancers. Funded by the Marie Skłodowska-Curie Actions programme, the VimAc project aims to investigate the stretchability of IFs, a fundamental feature that helps cells to adjust their shape without damage. Researchers will also study the interaction between vimentin IFs and actin filaments.
Objective
Many cellular processes, such as cell shape, mechanics, and intracellular transport, rely on the organization of and interactions between cytoskeletal filaments (CFs). Intermediate filaments (IFs) are the least studied CFs, with little knowledge of their interactions with other CFs, particularly actin filaments (AFs). Vimentin, one of the most abundant members of the IF family, is upregulated during epithelial-to-mesenchymal transition and in epithelial cancers, its expression is associated with poor prognosis. Their hierarchical structure gives them great stretchability, which aids cells under large deformations. However, little is known about the deformation-induced unfolding of alpha helices and the parameters that drive it. This study focuses on understanding the origin of vimentin IF (VIF) stretchability by providing direct visualization of the unfolding of alpha helices within the VIFs and transition to beta sheets upon stretching under various conditions. Interactions of VIFs with AFs play an important role in cell mechanics and successful mitosis. Yet, if these filaments interact directly is still a matter of debate. The proposed project focuses on the interaction between VIFs and AFs to determine whether they interact directly at the filament level and, if so, what are the strengths of the interactions and their binding/unbinding rates. A combination of approaches and methodologies will be used, including in vitro reconstituted filaments, optical tweezers, tip-enhanced Raman spectroscopy, computer simulation. The knowledge gained from this project will help understand crucial physiological and pathological processes. The host and supervisor are well-equipped for this project, with the supervisor's expertise in understanding IF mechanics and function as well as interaction between CFs utilizing a multiscale biophysical approach. The PF will establish a unique niche in biophysics research and a robust CV for future grant applications and research positions.
Fields of science
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- natural sciencesbiological sciencesbiophysics
- natural sciencesphysical sciencesopticsmicroscopyconfocal microscopy
- natural sciencesphysical sciencesopticsspectroscopy
- natural sciencesmathematicsapplied mathematicsmathematical model
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
37073 Gottingen
Germany