PhD Scientific Days 2019

Budapest, April 25–26, 2019

The impact of amyloid proteins on the morphology of the fibrin network

Feller, Tímea

Feller Tímea1 and Kellermayer Miklós S.Z.1
1 Semmelweis Egyetem Biofizikai és Sugárbiológiai Intézet, Budapest

Language of the presentation

English

Text of the abstract

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder, where amyloid-β peptides are deposited in the brain and in the brain vessels. Fibrin deposition is also increased in brains with AD. Clots formed from fibrin in the presence of amyloid-β peptides are structurally abnormal and resistant to lysis. The abnormal clots can occlude the blood vessels in the brain, thus contribute to the AD with a vascular component.
Aims: To uncover the mechanism, how amyloid can alter the morphology of the fibrin network and how does it influence the lysis of the clot.
Method: Aβ25-35 is the toxic fragment of the amyloid-β peptide that forms fibers on mica surface with epitaxial assembly mechanism. We mixed fibrinogen with Aβ25-35 and clotted it on a mica surface. We investigated the microstructure of the clots with Cypher AFM. We also investigated the mechanical properties of the clots with a nano-rheology measurement called nano-thrombelastography (nTEG), developed by our workgroup.
Results: The morphology of the Aβ25-35 fibers formed on mica can be finely tuned with the Aβ25-35 and KCl concentration. We observed fibrinogen accumulation right next to the amyloid fibers. We initiated the clotting of fibrinogen in the presence of 20 μM amyloid. The average height and width of the fibrin fibers in the formed network decreased significantly (18.0 nm (±5.09 nm) height instead of 21.8 nm (±5.47 nm), and 122.7 nm (±28.4 nm) width instead of 141.7 nm (±32.5 nm)). The nTEG showed an increased force difference in samples containing amyloid all through the clotting, both in platelet poor and platelet rich plasma. It could be due to the increased Young modulus of the individual fibers.
Conclusion: In the presence of amyloid peptides a fibrin network of smaller fibers is formed. It indicates an increased rigidity, in accordance with our nTEG measurements.

Data of the presenter

Basic and Translational Medicine Doctoral School