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Mechanobiology
Thrombolysis
Coagulation
Bioadhesion
Gene Therapy
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Bioadhesion

We have studied receptor-mediated bioadhesion in the context of blood coagulation and inflammation reactions under conditions of hemodynamic flow. This work has focused on:

  • Platelet and neutrophil homotypic and heterotypic aggregation.
  • Platelet GPIb adhesion to vWF.
  • PSGL-1/P-selectin adhesion: Neutrophil membrane tethering.
  • Thresholds in neutrophil string formation.
  • Red blood cell adhesion to platelets, neutrophils and fibrin.

In these studies, our laboratory has shown that neutrophil membrane tether extension prolongs the life of the PSGL-1/P-selectin bond life time. This demonstrates that membrane mechanics work in conjunction with bonding mechanisms to regulate bioadhesion. In other studies in collaboration with Dr. T. Diacovo, the clinical disease state of platelet type and type 2B von Willebrand disease is predicted by the long life time of the platelet GPIb-vWF A1 domain binding interactions.

Publications

P. Tandon, S. L. Diamond. "Hydrodynamic effects and receptor interactions of platelets and their aggregates in linear shear flow." Biophysical J. 73, 2819 (1997).

P. Tandon, S. L. Diamond. "Kinetics of b2-integrin and L-selectin bonding during neutrophil aggregation in shear flow." Biophysical J. 75, 3163 (1998).

S. L. Diamond, P. Tandon, D. Schmidtke, I. Laurenzi. "Cellular Aggregation in Blood Flow." Comments Theoretical Biol. 8, 1 (2000).

D. Schmidtke, S. L. Diamond. "Direct observation of membrane tethers formed during neutrophil attachment to adherent platelets or P-selectin in physiological shear flow." J. Cell. Biol. 179, 719 (2000).

E.Y.H. Park, M.J. Smith, E. S. Stropp, J. A. Diveietro, W. F. Walker, D.W. Schmidtke, S.L.Diamond, M.B. Lawrence. Comparison of PSGL-1 microbead and neutrophil rolling: Microvillus elongation stabilizes P-selectin clusters. Biophysical J. 82, 1835 (2002).

M. Frojmovic, G. Nash, S.L. Diamond. Cell Aggregation and Cell Adhesion in Flow. Thromb. Haem. 87, 771 (2002).

T. A. Doggett, G. Girdhar, A. Lawshe, D. W. Schmidtke, I. J. Laurenzi, S. L. Diamond, T. G. Diacovo. Selectin-like Kinetics and Biomechanics Promote Rapid Platelet Adhesion in Flow: The GPIb?-vWF Tether Bond. Biophysical J. 83, 194 (2002).

M. Goel, S. L. Diamond. Adhesion of normal erythrocytes to activated neutrophils, activated platelets, and fibrin polymerized from plasma at depressed venous shear rates. Blood. 100, 3739 (2002).

K.A. Kadash, M.B. Lawrence, S.L. Diamond. Neutrophil String Formation: Hydrodynamic thresholding and cell deformation during cell collisions. Biophysical J. 86:(2004).

Edmondson KE, Denney WS, Diamond SL: Neutrophil-bead collision assay: pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetime. Biophys J 2005, 89:3603-3614.

Ji JY, Jing H, Diamond SL. Hemodynamic regulation of inflammation at the endothelial-neutrophil interface. Ann Biomed Eng. 2008 Apr;36(4):586-95. Epub 2008 Feb 26.

 

 

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    Institute for Medicine & Engineering (IME)
    3340 Smith Walk
    1020 Vagelos Research Laboratories
    University of Pennsylvania
    Philadelphia, PA 19104-6383
    Lab No.: (215) 573-5704
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