Ziel
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.
Wissenschaftliches Gebiet
Thema/Themen
Aufforderung zur Vorschlagseinreichung
FP7-PEOPLE-2012-IOF
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
MC-IOF - International Outgoing Fellowships (IOF)Koordinator
32000 Haifa
Israel