Bionanotechnology Applications for Self-Assembling Fibres

Introduction:

Engineering 3D cell culture systems is a powerful and rapidly expanding multidisciplinary approach. Despite it being a relatively new field, it is already certain that its potential expands beyond pure academic interest showing considerable promise for regenerative medicine. Over the past five years we have described a designed peptide-based self-assembling fibre system, that we are currently developing as a scaffold for 3D cell culture; this involves forming fibre networks, recruiting bioactive molecules and increasing stability to make in vivo use of the SAFs possible.

Making Matrices:

In combination with standard SAFs, fibre shaping (FiSh) peptides can be used to introduce different morphologies into the fibres ( Ryadnov and Woolfson Angew. Chem. - Int. Ed. 42 3021-3023 ( Abstract), Ryadnov and Woolfson Nature Materials 2 329-332 ( Abstract)). The FiSh peptides are built around specially designed hubs to which two or three linear peptides can be appended. The linear peptides are based on the original designs, which each compromise two halves: A and B, or C and D, as shown below, these halves are mixed and matched to make FiSh peptides. Mixing the specialist peptides with standard SAFs result in shaping otherwise straight rod-like fibres into branched and kinked structures.

Ryadnov and Woolfson . J Am Chem Soc 126 7454-7455 (Abstract). The fibre recruiting (FiRe) peptides, like the FiSh peptides, work in conjunction with standard fibres to recruit active biomolecules on the surface of fibres, via a "bait" incorporated in the fibres. This might be used, for example, to mediate cell attachment to the scaffold.

We have successfully stabilized fibres to be used at physiological conditions and, with collaborators, are investigating their feasibility and comparability in 3D cell culture using a variety of cell lines. Also, we are widening our scope to include other novel peptide/protein-based self-assembling matrices.