Abstract
Various amyloid aggregates, in particular, aggregates of amyloid β-proteins, demonstrate in vitro and in vivo cytotoxic effects associated with impairment of cell adhesion. We investigated the effect of amyloid aggregates of smooth-muscle titin on smooth-muscle-cell cultures. The aggregates were shown to impair cell adhesion, which was accompanied by disorganization of the actin cytoskeleton, formation of filopodia, lamellipodia, and stress fibers. Cells died after a 72-h contact with the amyloid aggregates. To understand the causes of impairment, we studied the effect of the microtopology of a titin-amyloid-aggregate-coated surface on fibroblast adhesion by atomic force microscopy. The calculated surface roughness values varied from 2.7 to 4.9 nm, which can be a cause of highly antiadhesive properties of this surface. As all amyloids have the similar structure and properties, it is quite likely that the antiadhesive effect is also intrinsic to amyloid aggregates of other proteins. These results are important for understanding the mechanisms of the negative effect of amyloids on cell adhesion.
Highlights
Misfolding of proteins and their subsequent aggregation is a well-known pathological process associated with such diseases as amyloidoses [1,2]
We showed that amyloid aggregates of smooth-muscle titin caused the death of smooth-muscle cells
The obtained confocal microscopy data, such as the reorganization of the actin cytoskeleton, occurrence of filopodia, lamellipodia, and stress fibers indicated the impaired adhesion of smooth-muscle cells
Summary
Misfolding of proteins and their subsequent aggregation is a well-known pathological process associated with such diseases as amyloidoses [1,2]. They include Alzheimer’s and Parkinson’s diseases, type II diabetes, prion diseases, as well as systemic amyloidoses [3,4,5,6]. The toxic effect of various intermediaries of amyloid aggregates, including mature fibrils, on cells and the organism is considered to be the main danger of amyloid structures [7,8,9,10,11,12]. Particular β-sheets are organized perpendicular to the fibril main axis of growth
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