Synthetic ECMs

Cells are embedded in highly dynamic matrices (extracellular matrix) composed of complex networks of proteins and polysaccharides. The latter are particularly poorly characterized, in terms of structure, function and intermolecular interactions. Here, we aim to develop a platform that integrates synthetic chemistry with advanced manufacturing technologies to dissect the complexity and manufacture biomimetic analogues of these materials. Over the past years, the Delbianco’s group has used Automated Glycan Assembly (AGA) to synthesize well-defined natural as well as unnatural oligosaccharides to establish structure-property correlations. These compounds are ideal standards to characterize natural sourced materials and shed light on how the chemical structure affect the properties of the natural matrix. In addition, these samples provide a mean to produce artificial biomaterials with well-defined properties. To achieve these goals, the Toh’s group will converge microfluidic and 3D printing technologies, which offer the ability to screen different synthesis configurations using minute quantity of materials as well as scale the production and purification of the synthetic matrix.

To develop this platform, we selected bacterial biofilms as first target. Some bacteria are able to produce modified cellulose (phosphoethanolamine cellulose) as part of the protective biofilms they build in challenging environments. This modified cellulose forms a nanocomposite with amyloid curli fibres that protect the bacteria and confers elasticity to the biofilm, suggesting enormous potential for the production of novel bioinspired materials. Yet, no insights into the modification pattern of cellulose and its impact on biofilm formation exist, since isolation and purification from the microbial matrix are extremely hard. This project will realize a novel platform to characterize natural biofilms and manufacture artificial matrices with tunable material properties. The technology optimized within this project will be then implemented to study more complex mammalian glycosaminoglycan matrix systems.

 

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