Image-based analysis and simulation of the effect of platelet storage temperature on clot mechanics under uniaxial strain

Lee, Sang Joon John; Nguyen, Dustin M; Grewal, Harjot S; Puligundla, Chaitanya; Saha, Amit K.; Nair, Prajeeda M; Andrew, P.; Ramasubramanian, Anand K.

doi:10.1007/s10237-019-01203-8

Cited by 5 publications

(6 citation statements)

References 53 publications

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“…We show that the work done by contracting platelets in remodeling the fibrin fibers is stored as strain energy density even before an external load is applied and is a critical contribution to the mechanism by which the clots resist deformation ( 38 ). Analogous to macroscopically familiar structures such as a rope hammock or an anchor capstan, our experimental data and modeling support the hypothesis that the discrete prestressed nodes composed of fibrin-bound platelet aggregates are key to the structural stability of the clots ( 39 ) ( Fig. 6 D ).…”

Section: Discussionsupporting

confidence: 76%

Fibrin prestress due to platelet aggregation and contraction increases clot stiffness

Pathare¹,

Eng

Lee

et al. 2021

Biophysical Reports

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Section: Discussionsupporting

confidence: 76%

Fibrin prestress due to platelet aggregation and contraction increases clot stiffness

Pathare¹,

Eng

Lee

et al. 2021

Biophysical Reports

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“…Our simulations show that the fibers transverse to the direction of external load are under compressive stresses and they eventually buckle, while fibers longitudinal to the direction of external load are under tension and get stretched. This orientational anisotropy gives rise to spatial heterogeneity in microscale stress distributions that govern their overall behavior including nonlinear stiffness and tendency to rupture ( 76 , 77 ). The local heterogeneity in strain distribution also manifests as disordered patterns of force transmission through tensile force chains ( 26 , 27 , 78 ).…”

Section: Discussionmentioning

confidence: 99%

Clots reveal anomalous elastic behavior of fiber networks

Zakharov,

Awan,

Gopinath

et al. 2024

Sci. Adv.

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The adaptive mechanical properties of soft and fibrous biological materials are relevant to their functionality. The emergence of the macroscopic response of these materials to external stress and intrinsic cell traction from local deformations of their structural components is not well understood. Here, we investigate the nonlinear elastic behavior of blood clots by combining microscopy, rheology, and an elastic network model that incorporates the stretching, bending, and buckling of constituent fibrin fibers. By inhibiting fibrin cross-linking in blood clots, we observe an anomalous softening regime in the macroscopic shear response as well as a reduction in platelet-induced clot contractility. Our model explains these observations from two independent macroscopic measurements in a unified manner, through a single mechanical parameter, the bending stiffness of individual fibers. Supported by experimental evidence, our mechanics-based model provides a framework for predicting and comprehending the nonlinear elastic behavior of blood clots and other active biopolymer networks in general.

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“…Our simulations show that the fibers transverse to the direction of external load are under compressive stresses and they eventually bend and buckle; while fibers longitudinal to the direction of external load are under tension and get stretched. This orientational anisotropy gives rise to spatial heterogeneity in microscale stress distributions which govern their overall behavior including non-linear stiffness and tendency to rupture ( 66 ),( 67 ). The local heterogeneity in strain distribution also manifests as disordered patterns of force transmission through tensile force chains ( 17 ),( 18 ),( 68 ).…”

Section: Discussionmentioning

confidence: 99%

“…For a beam of circular cross-section, A = πr 2 , and I = πr 4 /4, and the expected bending to stretching ratio is then κ /( μl 0 2 ) = r 2 /(2 l 0 2 ). A fibrin fiber is estimated to be l 0 ≅ 10 μm long and 2 r ≅ 280 nm thick ( 22 ),( 66 ). Since fibrin is a bundle of protofibrils with bending modulus expected to be smaller than that of a uniform cylinder, we set the nondimensionalized ratio of bending to stretching stiffness parameter in the simulations to be κ * = k ·[ r 2 /(2 l 0 2 )], where r 2 /(2 l 0 2 ) is on the order of 10 -6 .…”

Section: Methodsmentioning

confidence: 99%

Clots reveal anomalous elastic behavior of fiber networks

Zakharov

Awan

Cheng

et al. 2023

Preprint

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The mechanical properties of many soft natural and synthetic biological materials are relevant to their function. The emergence of these properties from the collective response of the structural components of the material to external stress as well as to intrinsic cell traction, remains poorly understood. Here, we examine the nonlinear elastic behavior of blood clots by combining microscopy and rheological measurements with an elastic network model that accounts for the stretching, bending, and buckling of constituent fibrin fibers. We show that the inhibition of fibrin crosslinking reduces fiber bending stiffness and introduces an atypical fiber buckling-induced softening regime at intermediate shear, before the well-characterized stiffening regime. We also show that crosslinking and platelet contraction significantly alter force propagation in the network in a strain-dependent manner. Our mechanics-based model, supported by experiments, provides a framework to understand the origins of characteristic and anomalous regimes of non-linear elastic response not only in blood clots, but also more generally in active biopolymer networks.

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Image-based analysis and simulation of the effect of platelet storage temperature on clot mechanics under uniaxial strain

Cited by 5 publications

References 53 publications

Fibrin prestress due to platelet aggregation and contraction increases clot stiffness

Fibrin prestress due to platelet aggregation and contraction increases clot stiffness

Clots reveal anomalous elastic behavior of fiber networks

Clots reveal anomalous elastic behavior of fiber networks

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