title: Bioactive TTR105-115-based amyloid fibrils reduce the viability of mammalian cells.
abstract: A growing number of protein-based fibrous biomaterials have been produced with a cross-β amyloid core yet the long-term effect of these materials on cell viability and the influence of core and non-core protein sequences on viability is not well understood. Here, synthetic bioactive TTR1-RGD and control TTR1-RAD or TTR1 fibrils were used to test the response of mammalian cells. At high fibril concentrations cell viability was reduced, as assessed by mitochondrial reduction assays, lactate dehydrogenase membrane integrity assays and apoptotic biomarkers. This reduction occurred despite the high density of RGD cell adhesion ligands and use of cells displaying integrin receptors. Cell viability was affected by fibril size, maturity and whether fibrils were added to the cell media or as a pre-coated surface layer. These findings show that while cells initially interact well with synthetic fibrils, cellular integrity can be compromised over longer periods of time, suggesting a better understanding of the role of core and non-core residues in determining cellular interactions is required before TTR1-based fibrils are used as biomaterials.
authors: The ARC Dairy Innovation Hub, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, VIC 3010, Australia; Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Marie N
authors: MN
authors: Bongiovanni
authors: The ARC Dairy Innovation Hub, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, VIC 3010, Australia; Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: sgras@unimelb.edu.au.
authors: Sally L
authors: SL
authors: Gras
mesh_terms: D016475:3T3 Cells; D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; D001672:Biocompatible Materials; D015415:Biomarkers; D010455:Peptides
keywords: Apoptosis; Biocompatibility; Cell adhesion; MTT assay; RGD peptide