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RIGIDITY SENSING

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Mechanisms of Cellular Rigidity Sensing

Recent studies show that the rigidity of the extracellular matrix is a critical determinant of cell growth, differentiation, and death. Cells sense rigidity via integrin adhesions and respond by changing their morphology, signalin... ver más

01/10/2017

TECHNION ISRAEL I...

265K€

Presupuesto del proyecto: 265K€

Líder del proyecto

TECHNION ISRAEL INSTITUTE OF TECHNOLOGY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2017-10-01 No tenemos la información de la convocatoria

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TECHNION ISRAEL INSTITUTE O...

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Líder del proyecto

TECHNION ISRAEL INSTITUTE OF TECHNOLOGY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 265K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Recent studies show that the rigidity of the extracellular matrix is a critical determinant of cell growth, differentiation, and death. Cells sense rigidity via integrin adhesions and respond by changing their morphology, signaling, and gene expression patterns. Irregular rigidity signals or defective responses to appropriate rigidity signals underlie many medical disorders. This is especially evident in cancer, where the ability of cells to detect differences in matrix rigidity is fundamentally altered. Despite the importance of mechanosensing of matrix rigidity, findings in this field have been mainly phenomenological, and at the moment we still don’t know how rigidity sensing occurs. Active rigidity sensing involves development of traction forces on integrin adhesions, yet how cells develop forces, and how these forces are used to sense and transmit rigidity signals are both unknown. This grant is focused on analyses of the steps in building the machinery used by fibroblasts to sense and transmit rigidity signals. During the outgoing phase of the studies the applicant will use a combination of nanofabricated surfaces with integrin ligands, elastic micropillars that allow measuring forces, and super-resolution microscopy to define the critical steps in the assembly of integrin adhesions and to determine which proteins are essential for force production. The return phase of the studies will focus on investigating the signaling events downstream of rigidity sensing using biophysical measurements of the interaction kinetics of signaling molecules with integrin adhesions. The proposed studies will provide a detailed spatiotemporal description of the critical components and pathways of mechanosensing of matrix rigidity, and will help explain the underlying mechanisms involved in rigidity sensing during important processes such as differentiation or cancer.

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