Rupture of blood clots: Mechanics and pathophysiology

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Science Advances  26 Aug 2020:
Vol. 6, no. 35, eabc0496
DOI: 10.1126/sciadv.abc0496
  • Fig. 1 Rupture of cracked fibrin gel specimens.

    (A) Schematic of incipient rupture and embolization of an intravascular blood clot due to shear tractions of blood flow acting on its surface (dashed arrow), causing opening of a tensile crack. (B) Schematic of crack geometry showing a 30-mm-wide fibrin clot sample with an edge crack (a). (C) Crack propagation in a stretched plasma gel made with human blood plasma. Samples were stretched at 3 mm/min while recording force-displacement curves. (D and E) Representative fluorescence confocal microscopy images at the crack tip or far from the crack in the fibrin network that was unstrained (D) and stretched at 40% strain. (E) Images are all at the same gain and other microscope settings for comparison, showing the densification with stretching, except for the insets, where the brightness was increased to show fiber orientation. Fibrin gels were strained to 10, 20, and 40%. While still under tension, samples were immersed in fixative and then excised from the stretching device. (F) Fiber density, as measured by the mean fluorescence intensity (MFI), increased at the crack tip (<100 μm) with increasing strain (10 to 40%) and compared to areas removed from the crack tip (>1 mm). (G and H) Fibers showed increasing alignment (maximum order parameter = 1) under increasing strain at the crack tip, but not far from the crack. Statistical significance was determined by a one-way analysis of variance (ANOVA) followed by a Tukey multiple comparison test. ***P < 0.001. a.u., arbitrary unit.

  • Fig. 2 Quantitative characterization of toughness of fibrin gels.

    (A) Representative force-displacement curves at three different crack lengths (black) and a fibrin gel with no crack (gray). Results from data analysis to estimate (B) maximum force, (C) critical displacement, which corresponds to the displacement at the maximum force, and (D) critical energy release rate, all as a function of crack length.

  • Fig. 3 Material parameters of fibrin rupture and fitting to the model.

    (A) Force-displacement curve for a uniaxial test used to fit the parameters in the FE model. The unfolded proteins aggregate via hydrophobic interactions, expelling the water leading to a volume decrease. The FE model underestimates the amount of liquid lost (the reason is discussed in section S5). (B) Match between the force-displacement curves from the experiments and the finite element model predictions using the parameters fitted from (A) for crack lengths a* = 3.3 and 10.5 mm. The crack tip starts propagating when the overall displacement Δ = Δc. Δc decreases with the crack length a* (see Fig. 2B). Exp corresponds to the experimental results while FE corresponds to the finite element analysis. (C) Surface plots for maximum principal logarithmic strain when Δ = Δc. Strain concentration is observed near the crack. (D) Computation of energy release rate Gc. For crack lengths a* = 3.3 and 10.5 mm, Gc = 4.44 and 6.54 J/m*, respectively. The FE model is used to compute the potential energies for specimens with crack lengths a* ± δ stretched to Δ = Δc : Wc(a*), a* ± δ ] and Gc = − (1/t)∂Wc(a*), a]/∂aΔ = Δc, a = a*.

  • Fig. 4 Unfolding of fibrin monomers and alignment of fibrin fibers with stretching and their spatial distribution.

    (A) The fraction of unfolded monomers nu and alignment χ monotonically increase as the specimen is stretched near the crack tip (y = 0) and at the uncracked free surface (y = ymax). (B) Unfolded fraction nu and alignment χ as a function of horizontal distance y from the crack tip. (C and D) Surface plot of unfolded fraction nu and alignment χ. Notable unfolding and alignment are observed even away from the crack tip.

  • Fig. 5 Mechanism of rupture.

    (A) Strain component E2 versus distance from the crack y. (B) E2 at 100 μm from the crack tip when Δ = Δc. We compute the average of the data to conclude that the critical strain is 1.04. (C) Crack tip opening angle was determined using the ImageJ angle tool for measurement, where the angle was approximated at the center of the crack tip right before the onset of rupture (critical strain).

  • Fig. 6 The crack length is a*= 7.2 mm for these results.

    (A) Force-extension curves for various values of solid (fibrin) volume fraction (ϕ). (B) Logarithmic strain E2 versus distance from the crack tip y for various values of ϕS. (C) Variation of Gc versus ϕS.

Supplementary Materials

  • Supplementary Materials

    Rupture of blood clots: Mechanics and pathophysiology

    Valerie Tutwiler, Jaspreet Singh, Rustem I. Litvinov, John L. Bassani, Prashant K. Purohit, John W. Weisel

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    The PDF file includes:

    • Sections S1 to S12
    • Figs. S1 to S8
    • Legends for movies S1 and S2
    • References

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