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Keynote Lecture

Novel concepts of fibrous protein scaffolds for controlling cell interactions

Thursday (24.09.2020)
15:40 - 16:10 B: Biomaterials
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Cell growth is modulated by biochemical, topographical and mechanical signals in the extracellular matrix (ECM). This complex interplay makes the control of cell-material interactions one of the most important challenges in regenerative medicine. To understand the role of individual cues during cell material interactions, novel protein scaffold designs are required that can mimic selected aspects of the native ECM.

Therefore, we have developed different techniques to prepare nanofibrous protein scaffolds with controlled molecular composition, nanotopography and hierarchical arrangement. One of our key methods is the extrusion of proteins through ceramic nanopores.1 With this method we established a new in vitro model system to study fibrillogenesis of fibronectin in a cell-free environment.2 Moreover, using molecular dynamics simulations, we found out that the phosphorylation of fibronectin influences the flexibility of the molecule (see Fig. 1).3 These findings could become an important aspect for understanding mechanotransduction of cells in vivo and for unravelling fibrillogenesis of fibronectin in vitro.

With salt-induced self-assembly we recently found a new mechanism to prepare fibrinogen nanofibers in a cell- and enzyme-free environment. Depending on the substrate material, our process offers the unique ability to produce either free-standing or immobilized matrices (see Fig. 2).4 Analysis of the protein conformation in fibrinogen scaffolds revealed changes in the secondary structure, which were correlated with morphological transitions.5 This conformational transition was not associated with any pathogenic amyloid formation. These properties make our novel fibrinogen scaffolds extremely attractive for future applications in regenerative medicine.

To study topography-related changes of cell growth in real time, we introduced a new process, which yields nanofibrous and planar topographies in a single protein scaffold. By combining polymer patterning with self-assembly of nanofibers, we fabricated collagen and fibrinogen scaffolds with spatially controlled variations in the surface topography.6 First studies with fibroblasts on patterned collagen scaffolds showed that spatially controlled topography variations induced changes in the cell size and morphology.

With our novel methods to prepare nanofibrous protein scaffolds, we have established a versatile biophysical toolbox to study the role of individual signals during cell-material interaction in vitro.

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