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Prof. Manuel Salmerón-Sánchez, Material-driven fibronectin fibrillogenesis

Date: 4 October 2012   Time: 14:45 - 15:30

Prof. Manuel Salmerón-Sánchez
Universitat Politècnica de València, Spain

Material-driven fibronectin fibrillogenesis

Abstract:
Fibronectin (FN) is a cell-adhesive glycoprotein that contains three types of repeating modules (types I, II and III). Most cells assemble rich FN matrices via an integrin-dependent contractile process that incorporates FN molecules into matrix fibrils, through binding of I1-5 either to III1-2 or III12-14 domains. Significant efforts have focused on engineering materials that recapitulate characteristics of ECM.
However, materials-based approaches to reconstitute the network structure and bioactivity of FN fibrillar matrices have not been established. We have shown that adsorption of individual FN molecules onto particular surface chemistries would induce exposure of self-assembly sites to drive FN fibril assembly and identified poly(ethyl acrylate) (PEA) as a potential surface chemistry to generate FN fibrils. The 70 kDa amino-terminal regions are essential for cell-mediated FN assembly. This domain is not accessible in the folded, compact structure of FN in solution and a conformational change of the molecule is mandatory for physiological matrix assembly to occur. Strikingly, material-driven fibrillogenesis absolutely requires the 70 kDa amino-terminal region of FN.
Given its similarities with the physiological assembly of FN, the material-driven FN fibrillogenesis is expected to yield a protein network with enhanced biological activity; indeed, the conformation adopted by the protein should promote the exposure of domains that favor the interaction with cells and other proteins. The material-driven FN network formed upon passive adsorption on surface chemistries such as PEA is endowed with a distinctive biological activity, since it was shown to support enhanced cell adhesion, matrix secretion and degradation, and to affect also higher order cellular functions such as cell differentiation. The improved biological properties of this artificial FN network confirm the similarity of this cell-free fibrillogenesis process and of the resulting network structure with the physiological FN fibrils, paving the way for its exploitation to control and direct cell behavior in more complex systems mimicking natural tissues and cell microenvironments.

Location:  SEMS Seminar Room
Contact:  Prof Gleb Sukhorukov
Email:  g.sukhorukov@qmul.ac.uk