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Vimentin intermediate filaments: the origin of stretchability and their direct interaction with actin filaments

Descripción del proyecto

Información sobre la mecánica y las interacciones de los elementos del citoesqueleto

Los filamentos del citoesqueleto son estructuras dinámicas que dan forma, soporte y organización a las células. Constan de tres tipos principales: microfilamentos, filamentos intermedios (FI) y microtúbulos, cada uno de los cuales desempeña distintas funciones en el movimiento celular, la división y el transporte intracelular. Los FI, en particular la vimentina,se han estudiado menos estudiados a pesar de su papel emergente en los cánceres epiteliales. El equipo del proyecto VimAc, financiado por las Acciones Marie Skłodowska-Curie, pretende investigar la capacidad de estiramiento de los FI, una característica fundamental que ayuda a las células a ajustar su forma sin sufrir daños. Los investigadores también estudiarán la interacción entre los FI de vimentina y los filamentos de actina.

Objetivo

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.

Ámbito científico (EuroSciVoc)

CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural. La clasificación de este proyecto ha sido validada por su equipo.

Coordinador

GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS
Aportación neta de la UEn
€ 189 687,36
Dirección
WILHELMSPLATZ 1
37073 Gottingen
Alemania

Ver en el mapa

Región
Niedersachsen Braunschweig Göttingen
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos