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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Bongiovanni MN,Gras SL

doi

10.1016/j.biomaterials.2014.12.039

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

105-16

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(14)01289-7

journal_volume

46

pub_type

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