Endogenously generated amyloid-β increases stiffness in human neuroblastoma cells

Area of Science:

• Neuroscience
• Cell Biology
• Biophysics

Background:

• Amyloid-beta (Aβ) is known to be toxic to neurons.
• Aβ deposition and aggregation can disrupt neuronal function.
• The effect of Aβ on neuronal cell stiffness is unknown.

Purpose of the Study:

• To investigate whether endogenous Aβ overexpression alters neuronal cell stiffness.
• To determine the role of Aβ in changes to cell stiffness.
• To explore potential therapeutic strategies targeting Aβ-induced stiffness.

Main Methods:

• Used human neuroblastoma cells overexpressing amyloid precursor protein (APP) and its Swedish mutant (APPswe).
• Measured changes in cell stiffness using biophysical techniques.
• Administered γ-secretase inhibitor (DAPT) and tromethamine to modulate Aβ levels and calcium channel activity.

Main Results:

• Cells overexpressing APP or APPswe exhibited increased stiffness compared to controls.
• Reducing Aβ levels with DAPT decreased cell stiffness.
• Blocking Aβ-formed calcium channels with tromethamine also reduced cell stiffness.

Conclusions:

• Amyloid-beta (Aβ), not APP, is the primary contributor to increased neuronal cell stiffness.
• Modulating Aβ calcium channels can alleviate the impact of Aβ on membrane stiffness.
• Findings suggest Aβ-induced stiffness is a key factor in neuronal dysfunction.