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Integrin specificity in rigidity sensitive proliferation, activation and directional migration of endothelial cells

Objective

Cells have the extraordinary ability to regulate their morphology, functions and fate to minimal changes in the extracelullar microenvironment. Through multi-protein, cell-matrix adhesions they are able to recognize and respond not only to the chemical diversity of the extracellular matrix (ECM), but also to its physical and topographical features. Mechanical and structural cues encoded in the ECM have an essential role in healthy tissue function where contractility, spreading and proliferation are intricately regulated by cell-cell and cell-matrix adhesion and tension. Unsurprisingly, abnormal ECM mechanics are directly associated with disease and tissue malformation (atherosclerosis, wound healing and tumor formation). Understanding the mechanisms cells use to sense and transduce mechanical signals, as well as the contribution of key players in the process is a pressing, unmet challenge.
To achieve this goal, I here propose the development of an in vitro strategy that allows precise regulation of both biochemical and mechanical parameters in order to isolate their contribution on fundamental endothelial cell (EC) functions. The proposed work will exploit advances in materials science and nanotechnology to modulate with high precision the presentation of highly selective integrin ligands at the nanometer and micrometer length scales, on substrates with tunable viscoelasticity and mechanics. The anticipated effects of integrin engagement and substrate mechanics on ECs will shed light on how the microenvironment affects their proliferation, activation and directional migration, and help correlate these finding with pathological scenarios where blood vessel mechanics and EC integrin expression are deregulated. In summary, the proposed interdisciplinary approach will contribute both advanced tools to study cells in vitro and crucial answers for specific questions relating to EC biology.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 171 460,80
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 171 460,80
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