Laser-induced Propagation and Destruction of Amyloid β Fibrils

Abstract

The amyloid deposition of amyloid ␤ (A␤) peptides is a critical pathological event in Alzheimer disease (AD). Preventing the formation of amyloid deposits and removing preformed fibrils in tissues are important therapeutic strategies against AD. Previously, we reported the destruction of amyloid fibrils of ␤ 2 -microglobulin K3 fragments by laser irradiation coupled with the binding of amyloid-specific thioflavin T. Here, we studied the effects of a laser beam on A␤ fibrils. As was the case for K3 fibrils, extensive irradiation destroyed the preformed A␤ fibrils. However, irradiation during spontaneous fibril formation resulted in only the partial destruction of growing fibrils and a subsequent explosive propagation of fibrils. The explosive propagation was caused by an increase in the number of active ends due to breakage. The results not only reveal a case of fragmentation-induced propagation of fibrils but also provide insights into therapeutic strategies for AD.

Failure of Aβ(1-40) amyloid fibrils under tensile loading

“…We specifically find that amyloid fibrils approaching the micrometer scale are mechanically weak elements, highlighting an inherent tendency to break, perhaps even under thermal fluctuations, potentially explaining the significant contributions of fragmentation mechanisms to the kinetics of fibril growth [8]. The importance of amyloid fibril fragmentation for growth and aggregation has been experimentally demonstrated by laser induced destruction of amyloid β fibrils, which resulted in an explosive propagation of a larger number of fibrils and plaque formation [43]. The occurrence of enhanced breakage processes increases the density of the ends at which the growth occurs and favors the proliferation of new fibrils.…”

“…Several experimental techniques, based on the mechanical manipulation of the individual nanostructures, have been used to measure elastic modulus and strength [8,[35][36][37][38][39][40][41], and even provided a first experimental evaluation of the failure stress in the range of 0.2-1.0 GPa [8]. Recently, other experimental works based on sonication [42] and laser-induced shock wave propagation and destruction [43] have revealed a heightened tendency to breakage, and clarified some aspects of the kinetics of proliferation of amyloid fibrils. The observed high fragility of amyloid fibrils combined with the elongation mechanism that occurs only at the tails of each fibril, explain the explosive proliferation of the amyloid fibrils observed during laser irradiation due to the increased density of fibril terminals that accelerate growth [8,43].…”

“…Recently, other experimental works based on sonication [42] and laser-induced shock wave propagation and destruction [43] have revealed a heightened tendency to breakage, and clarified some aspects of the kinetics of proliferation of amyloid fibrils. The observed high fragility of amyloid fibrils combined with the elongation mechanism that occurs only at the tails of each fibril, explain the explosive proliferation of the amyloid fibrils observed during laser irradiation due to the increased density of fibril terminals that accelerate growth [8,43]. The understanding of proliferation mechanisms is fundamental not only for material science applications, but also for biomedicine, which faces issues related to deposition and uncontrolled self-assembly of amyloids in the form of large plaques with dimensions on the order of micrometers.…”

Destruction of Amyloid Fibrils of Keratoepithelin Peptides by Laser Irradiation Coupled with Amyloid-specific Thioflavin T

“…At 37°C, the fluorescence increased gradually for the C110 -131 peptide but not at all for the H110 -131 peptide. We then added NaCl and SDS, which are known to enhance fibril growth (22,24). The intensity of ThT fluorescence of both these peptides increased markedly in the presence of 100 mM NaCl and 0.5 mM SDS (Fig.…”

“…Using this method, we previously observed the laser irradiation-dependent inhibition of ␤ 2 -microglobulin fibril growth and the destruction of preformed fibrils of K3, a 22-residue peptide of ␤ 2 -microglobulin (23). More recently, we examined the effects of laser irradiation on the formation of A␤(1-40) fibrils (24). As was the case for K3 fibrils, extensive irradiation destroyed the preformed A␤ fibrils.…”