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1.
Journal of Biomedical Engineering ; (6): 876-885, 2023.
Artículo en Chino | WPRIM | ID: wpr-1008912

RESUMEN

In resting platelets, the 17 th domain of filamin a (FLNa17) constitutively binds to the platelet membrane glycoprotein Ibα (GPIbα) at its cytoplasmic tail (GPIbα-CT) and inhibits the downstream signal activation, while the binding of ligand and blood shear force can activate platelets. To imitate the pull force transmitted from the extracellular ligand of GPIbα and the lateral tension from platelet cytoskeleton deformation, two pulling modes were applied on the GPIbα-CT/FLNa17 complex, and the molecular dynamics simulation method was used to explore the mechanical regulation on the affinity and mechanical stability of the complex. In this study, at first, nine pairs of key hydrogen bonds on the interface between GPIbα-CT and FLNa17 were identified, which was the basis for maintaining the complex structural stability. Secondly, it was found that these hydrogen bonding networks would be broken down and lead to the dissociation of FLNa17 from GPIbα-CT only under the axial pull force; but, under the lateral tension, the secondary structures at both terminals of FLNa17 would unfold to protect the interface of the GPIbα-CT/FLNa17 complex from mechanical damage. In the range of 0~40 pN, the increase of pull force promoted outward-rotation of the nitrogen atom of the 563 rd phenylalanine (PHE 563-N) at GPIbα-CT and the dissociation of the complex. This study for the first time revealed that the extracellular ligand-transmitted axial force could more effectively relieve the inhibition of FLNa17 on the downstream signal of GPIbα than pure mechanical tension at the atomic level, and would be useful for further understanding the platelet intracellular force-regulated signal pathway.


Asunto(s)
Filaminas/metabolismo , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Simulación de Dinámica Molecular , Ligandos , Unión Proteica , Plaquetas/metabolismo , Factor de von Willebrand/metabolismo
2.
Journal of Medical Biomechanics ; (6): E439-E443, 2010.
Artículo en Chino | WPRIM | ID: wpr-803700

RESUMEN

Objective To analyze the energy of rolling manipulation in different frequency bands and find the features of rolling manipulation dynamics. MethodThe force signals of rolling manipulation of six experts and six beginners were measured and divided into different frequency bands by wavelet transform to calculate the energy. Through statistical analysis, 18 characteristic quantities of horizontal force or vertical force were created and the overall evaluation coefficient R was proposed. ResultsAbout 70% of experts’ rolling manipulation energy was found in 0~0.406 25 Hz and about 20% energy in 1.625~3.25 Hz. The overall evaluation coefficient R of 6 experts was over 0.70, while R of beginners was below 0.70, which showed the difference was significant. ConclusionsThe energy distribution of rolling manipulation reflects the characteristics of softness and periodicity. If the rolling manipulation is in accordance with the manipulative requirement and the overall evaluation coefficients R is over 0.70, it could be said that the operator masters the rolling manipulation well.

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