Enhancement of Cytoskeletal Tension Promotes Amyloid-β Aggregation on the Neuronal Cell Surface.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the majority of dementia cases. The accumulation of amyloid-β (Aβ) aggregates on neuronal surfaces is a known important event that typifies AD. Although cell membrane architecture and cytoskeletal tension are thought to be involved in the process of Aβ aggregation, it remains unclear how cytoskeleton-derived tension alters the function of cell membranes, which serve as a scaffold for Aβ aggregation. In this study, we investigated whether cytoskeletal tension promotes Aβ aggregation on neuroblastoma, SH-SY5Y cells. Cytoskeletal tension was enhanced by jasplakinolide, an actin depolymerization inhibitor, and calyculin A, a serine/threonine phosphatase inhibitor that promotes myosin II activation. Real-time imaging with quantum-dot-labeled Aβ nanoprobes revealed that both pharmacological treatments significantly increased Aβ deposition on the surface of living cells. Our findings suggest that cytoskeletal tension promotes Aβ aggregation over the membrane barrier, providing new insights into the biophysical mechanisms underlying Aβ accumulation in AD pathogenesis.