Biomedical Engineering Seminar

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"Blood Clot Structure and Mechanics From Nanometers to Centimeters"

John W. Weisel, PhD
Department of Cell and Developmental Biology
University of Pennsylvania School of Medicine

A new field of biomedical research, biomechanics of hemostasis and thrombosis, has been quickly developing over the past few years. The mechanical properties of fibrin are essential in vivo for the ability of clots to stop bleeding in flowing blood but also determine the likelihood of obstructive thrombi that cause heart attack and stroke. Despite such critical importance, the structural basis of clot mechanics is not well understood. This seminar will focus on recent biomechanical research on both platelet aggregation/adhesion and fibrin clots. An optical trap system has been developed to study protein-protein binding/unbinding at the single molecule level, and used to characterize fibrinogen-integrin interactions that are responsible for platelet aggregation. The results of this research are relevant to the behavior of platelets in flowing blood. Through studies of the structure and mechanical behavior of fibrin clots at the macroscopic, network, fiber and molecular levels, we show that they can only be understood by integration of their materials properties at all these levels and propose a molecular basis for their remarkable extensibility and compressibility. Basic features of the mechanisms uncovered include fiber alignment and bundling with stretching, followed by unfolding of some fibrin domains, exposing hydrophobic regions, which aggregate, expelling water. The mechanical unraveling of fibrin(ogen) was shown to be determined by molecular transitions that couple reversible extension-contraction of the α -helical coiled-coil regions with unfolding of the terminal γ-nodules. The coiled-coils act as molecular springs to buffer external mechanical perturbations, transmitting and distributing force as the γ-nodules unfold. All-atom Molecular Dynamics simulations further showed a transition from α-helix to β-sheet at higher extensions. Fourier Transform infrared spectroscopy of hydrated fibrin clots revealed the force-induced α- helix to β-sheet transition in fibrin experimentally. These regimes of forced elongation of fibrin provide important qualitative and quantitative characteristics of the molecular mechanisms underlying fibrin mechanical properties at the microscopic and macroscopic scales. The long-term goal is eventually to relate these basic science discoveries to thrombolysis, embolization, bleeding, thrombotic disorders, wound healing, angioplasty and methods of clot ablation and removal, and application of fibrin sealants.


  • Workflow Status:Published
  • Created By:Floyd Wood
  • Created:11/21/2012
  • Modified By:Fletcher Moore
  • Modified:10/07/2016