Clots reveal anomalous elastic behavior of fiber networks

Zakharov, Andrei; Awan, Myra; Gopinath, Arvind; Lee, Sang-Joon John; Ramasubramanian, Anand K.; Dasbiswas, Kinjal

doi:10.1126/sciadv.adh1265

Cited by 11 publications

(2 citation statements)

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“…Future theoretical efforts can explore different rules for spectrin rebinding and the effects on the connectivity of the actin-spectrin meshwork. Furthermore, buckling of spectrin edges can be considered as on a recent model of a network of fibrin fibers, which shows the importance of buckling for describing shear response int he network ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamic mechanisms for membrane skeleton transitions

Bonilla-Quintana,

Ghisleni,

Gauthier

et al. 2024

Preprint

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The plasma membrane and the underlying skeleton form a protective barrier for eukaryotic cells. The molecules forming this complex composite material constantly rearrange under mechanical stress to confer this protective capacity. One of those molecules, spectrin, is ubiquitous in the membrane skeleton and primarily located proximal to the inner leaflet of the plasma membrane and engages in protein-lipid interactions via a set of membrane-anchoring domains. Spectrin is linked by short actin filaments and its conformation varies in different types of cells. In this work, we developed a generalized network model for the membrane skeleton integrated with myosin contractility and membrane mechanics to investigate the response of the spectrin meshwork to mechanical loading. We observed that the force generated by membrane bending is important to maintain a smooth skeletal structure. This suggests that the membrane is not just supported by the skeleton, but has an active contribution to the stability of the cell structure. We found that spectrin and myosin turnover are necessary for the transition between stress and rest states in the skeleton. Our model reveals that the actin-spectrin meshwork dynamics are balanced by the membrane forces with area constraint and volume restriction promoting the stability of the membrane skeleton. Furthermore, we showed that cell attachment to the substrate promotes shape stabilization. Thus, our proposed model gives insight into the shared mechanisms of the membrane skeleton associated with myosin and membrane that can be tested in different types of cells.

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Section: Discussionmentioning

confidence: 99%

Dynamic mechanisms for membrane skeleton transitions

Bonilla-Quintana,

Ghisleni,

Gauthier

et al. 2024

Preprint

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“…The elasticity (or stiffness) is characterized by a reversible mechanical deformation, whereas the viscosity (or plasticity) is a slow irreversible deformation (creep). The mechanical properties of fibrin are essential for its functions [ 6 , 7 ]. In hemostasis, the clot must form a plug to stop bleeding and this structure must be strong enough to withstand the pressure of arterial blood flow.…”

Section: Introductionmentioning

confidence: 99%

Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA

Ullah,

Mirshahi,

Valinattaj Omran

et al. 2024

Cancers

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Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots’ permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis.

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