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Abstract Deep vein thrombosis (DVT) is a life‐threatening blood clotting condition that, if undetected, can cause deadly pulmonary embolisms. Critical to its clinical management is the ability to rapidly detect, monitor, and treat thrombosis. However, current diagnostic imaging modalities lack the resolution required to precisely localize vessel occlusions and enable clot monitoring in real time. Here, we rationally design fibrinogen‐mimicking fluoropeptide nanoemulsions, or nanopeptisomes (NPeps), that allow contrast‐enhanced ultrasound imaging of thrombi and synchronous inhibition of clot growth. The theranostic duality of NPeps is imparted via their intrinsic binding to integrins overexpressed on platelets activated during coagulation. The platelet‐bound nanoemulsions can be vaporized and oscillate in an applied acoustic field to enable contrast‐enhanced Doppler ultrasound detection of thrombi. Concurrently, nanoemulsions bound to platelets competitively inhibit secondary platelet–fibrinogen binding to disrupt further clot growth. Continued development of this synchronous theranostic platform may open new opportunities for image‐guided, non‐invasive, interventions for DVT and other vascular diseases.
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Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots
Abstract While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction or retraction . Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. Recently, blood clot contraction was observed to be hindered in patients with COVID-19. A three-dimensional multiscale computational model is developed and used to quantify biomechanical mechanisms of the kinetics of clot contraction driven by platelet-fibrin pulling interactions. These results provide important biological insights into contraction of platelet filopodia, the mechanically active thin protrusions of the plasma membrane, described previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach described can potentially apply to studying other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness.
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- PAR ID:
- 10464594
- Date Published:
- Journal Name:
- Communications Biology
- Volume:
- 6
- Issue:
- 1
- ISSN:
- 2399-3642
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s42003-023-05240-z
