Insulin amyloid structures and their influence on neural cells

Area of Science:

• Biochemistry
• Neuroscience
• Cell Biology

Background:

• Peptide aggregation into amyloid fibrils is linked to neurodegenerative diseases, diabetes, and systemic amyloidoses.
• Understanding the molecular basis of protein amyloid disorders requires studying the interaction of amyloid forms with neural cells.

Purpose of the Study:

• To investigate the effects of insulin amyloid fibrils on human neuroblastoma (SH-SY5Y) cells in vitro.
• To correlate the degree of insulin fibrillization with cellular changes and morphology.

Main Methods:

• Controlled kinetic fibrillization of insulin at low pH and elevated temperature.
• Multiscale characterization using fluorescence microscopy and multimodal scanning probe microscopy (SPM).
• Quantification of cell number, morphology, and analysis of aggregate-cell membrane interactions.

Main Results:

• Insulin aggregates progressively modify and decrease the number of neuroblastoma cells, correlating with fibrillization extent.
• SPM revealed that aggregates interact strongly with cell membranes, forming a rigid casing.
• This interaction may increase cell membrane stiffness and impair metabolic exchanges, causing a 40% cell drop after 48h.

Conclusions:

• Insulin amyloid fibrils induce significant detrimental effects on neuroblastoma cells in vitro.
• The interaction with cell membranes, leading to increased stiffness and impaired function, is a key mechanism of toxicity.
• These findings contribute to understanding the molecular pathology of amyloid-related disorders in neural tissues.