Functionalised amyloid fibrils for roles in cell adhesion.
We describe experiments designed to explore the possibility of using amyloid fibrils as new nanoscale biomaterials for promoting and exploiting cell adhesion, migration and differentiation in vitro. We created peptides that add the biological cell adhesion sequence (RGD) or a control sequence (RAD) to the C-terminus of an 11-residue peptide corresponding to residues 105-115 of the amyloidogenic protein transthyretin. These peptides readily self-assemble in aqueous solution to form amyloid fibrils, and X-ray fibre diffraction shows that they possess the same strand and sheet spacing in the characteristic cross-beta structure as do fibrils formed by the parent peptide. We report that the fibrils containing the RGD sequence are bioactive and that these fibrils interact specifically with cells via the RGD group displayed on the fibril surface. As the design of such functionalized fibrils can be systematically altered, these findings suggest that it will be possible to generate nanomaterials based on amyloid fibrils that are tailored to promote interactions with a wide variety of cell types.
Gras
Sally L
SL
Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville VIC 3010, Australia. sgras@unimelb.edu.au
Tickler
Anna K
AK
Squires
Adam M
AM
Devlin
Glyn L
GL
Horton
Michael A
MA
Dobson
Christopher M
CM
MacPhee
Cait E
CE
D016475:3T3 Cells; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002448:Cell Adhesion; D002477:Cells / Q000166:cytology* / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D014961:X-Ray Diffraction
D000682:Amyloid; D008024:Ligands; D010455:Peptides