Cellular and Molecular Biomechanics, Protein-Protein Interactions

Combining numerical simulation and biophysical techniques such as the optical trap and the micropipette aspiration technique, my laboratory seeks to understand how human leukocytes or cancer cells roll stably on the endothelium and migrate out of blood vessels. Cell rolling, which is recognized as the first key step for cellular migration into infected tissues, lymph nodes, aortic tissues, and cancer metastatic sites, is a complicated dynamic process mediated cooperatively by shear stress due to the blood flow, adhesion molecules expressed on rolling cells, leukocytes, and endothelial cells, as well as mechanical properties of these cells. This process has been implicated in inflammatory, infectious, cardiovascular, and cancerous diseases.

My laboratory also seeks to understand the role of von Willebrand factor (VWF) in hemostasis and thrombosis. VWF function depends on enzymatic VWF cleavage, which is enhanced by shear stress and many other factors. Excessive VWF cleavage results in von Willebrand disease, a potentially-fatal bleeding disorder, whereas insufficient VWF cleavage results in thrombotic thrombocytopenic purpura, a disease characterized by microvascular thrombosis.

Our research is supported by the National Institutes of Health, the American Heart Association, the Whitaker Foundation, Medical Implant Mechanics LLC, and the Barnes-Jewish Foundation.




Peer Reviewed Journals

       Liu B and JY Shao. 2014. Micropipette Aspiration and Subcellular Biophysics. CRC Handbook of Imaging in Biological Mechanics, ed. Neu C and G Genin. Taylor & Francis Press, Boca Raton, FL. In Press.

       Liu B and JY Shao. 2012. Tangential Tether Extraction and Spontaneous Tether Retraction of Human Neutrophils. Biophysical Journal. 103:2257-2264. PMCID: PMC3514515.

       Chen Y, DK Yao and JY Shao. 2010. The constitutive equation for membrane nanotube formation. Ann. Biomed. Eng. 38:3756-3765.

       Ying J, Y Ling, LA Westfield, JE Sadler and JY Shao. 2010. Unfolding the A2 domain of von Willebrand factor with the optical trap. Biophysical Journal. 98:1685-1693. PMCID: PMC2856187

       Shao JY. 2009. Biomechanics of leukocyte and endothelial cell surface. In Current Topics in Membranes, ed. Klaus Ley, Elsevier Inc. 25-45.

       Chen Y, B Liu, G Xu and JY Shao. 2009. Validation, in-depth analysis, and modification of the micropipette aspiration technique. Cell. Mol. Bioeng. 2:351-365. PMCID: PMC2843006.

       Liu B, Y Yu, DK Yao and JY Shao. 2009. A direct micropipette-based calibration method for AFM cantilevers. Rev. Sci. Instrum. 80:065109. PMCID: PMC2832057.

       Xu G and JY Shao. 2008. Human neutrophil surface protrusion: viscoelasticity and cytoskeletal involvement. Am. J. Physiol. Cell Physiol. 295:C1434-C1444.

       Yao DK and JY Shao. 2008. A novel technique of quantifying flexural stiffness of rod-like structures. Cell. Mol. Bioeng. 1:75-83. PMCID: PMC2843005.

       Girdhar G and JY Shao. 2007. Simultaneous tether extraction from endothelial cells and leukocytes: observation, mechanics, and significance. Biophysical Journal. 93:4041-4052.

       Xu G and JY Shao. 2007. Human neutrophil surface protrusion: viscoelasticity and cytoskeletal involvement. Biophysical Journal. In preparation.

       Girdhar G and JY Shao. 2007. Simultaneous tether extraction from endothelial cells and leukocytes. Biophysical Journal. In press.

       Yao DK and JY Shao. 2007. Flexibility of single microvilli on live neutrophils and lymphocytes. Physical Review E. 72:021907(6 pages).

       Liu B, CJ Goergen and JY Shao. 2007. Effect of temperature on tether extraction, surface extension, and cortical tension of human neutrophils. Biophysical Journal. In press.

       Chen Y, G Girdhar and JY Shao. 2007. Single membrane tether extraction from adult and neonatal dermal microvascular endothelial cells. Am. J. Physiol. Cell Physiol. 292:C1272-C1279.

       Shao JY and G Xu. 2007. The adhesion between a microvillus-bearing cell and a ligand-coated substrate: a Monte Carlo study. Ann. Biomed. Eng. 35:397-407.

       Girdhar G, Y Chen and JY Shao. 2007. Double tether extraction from human umbilical vein and dermal microvascular endothelial cells. Biophysical Journal. 92:1035-1045.

       Yu Y and JY Shao. 2007. Simultaneous tether extraction contributes to neutrophil rolling stabilization: a model study. Biophysical Journal. 92:418-429.

       Shao JY, Y Yu and ML Dustin. 2005. A model for CD2/CD58-mediated adhesion strengthening. Annals of Biomedical Engineering. 33:483-493.

       Xu G and JY Shao. 2005. Double tether extraction from human neutrophils and its comparison with CD4+ T lymphocytes. Biophysical Journal. 88:661-669.

       Girdhar G and JY Shao. 2004. Membrane tether extraction from human umbilical vein endothelial cells and its implication in leukocyte rolling. Biophysical Journal. 87:3561-3568.

       Shao JY, G Xu and P Guo. 2004. Quantifying cell-adhesion strength with micropipette manipulation: principle and application. Frontiers in Bioscience. 9:2183-2191.

       Shao, JY and J Xu. 2002. A modified micropipette aspiration technique and its application to tether formation from human neutrophils. J. Biomech. Eng. 124:388-396.

       Shao, JY. 2002. Finite element analysis of imposing femtonewton forces with micropipette manipulation. Ann. Biomed. Eng. 30:546-554.

       Shao JY and RM Hochmuth. 1998. Mechanical anchoring strength of L-selectin, b2 integrins and CD45 to neutrophil cytoskeleton and membrane. Biophysical Journal. 77:587-596.

       Shao JY, HP Ting-Beall and RM Hochmuth. 1998. Static and dynamic lengths of neutrophil microvilli. Proc. Natl. Acad. Sci. USA. 95:6797-6802.

       Shao JY and RM Hochmuth. 1997. The resistance to flow of individual human neutrophils in glass capillary tubes with diameters between 4.65 and 7.75 m. Microcirculation. 4:61-74.

       Shao JY, ZY Yan, FY Zhuang and RJ Sun. 1997. A two-parameter model for three types of nuclepore filtration of leukocytes. Journal of Applied Mathematics and Mechanics. 18:251-258.

       Shao JY and RM Hochmuth. 1996. Micropipette suction for measuring piconewton forces of adhesion and tether formation from neutrophil membranes. Biophysical Journal. 71:2892-2901.

       Hochmuth RM, JY Shao, J Dai and MP Sheetz. 1996. Deformation and flow of membrane into tethers extracted from neuronal growth cones. Biophysical Journal. 70:358-369.

       Shao JY, WY Wu and WQ Lu. 1994. Finite element analysis of the entry flow into a circular tube at low, moderate, and high Reynolds numbers. Journal of Hydrodynamics. 9(Ser. A): 531-540. (in Chinese with English abstract)

       Yan ZY, JY Shao, MQ Qian, WL Weng, Y Wang and JG Liu. 1993. The radius effect correction for the measurement of the whole blood viscosity using the capillary viscometer. Acta Scientiarum Naturalium Universitatis Pekinensis. 29:315-321. (in Chinese with English abstract)

       Shao JY, ZY Yan, WL Weng and Y Wang. 1992. Statistical analysis of the experimental results of erythrocyte suspension's micropore filtration for two diseases. Journal of Beijing Biomedical Engineering. 11:1-5. (in Chinese)


Invited Review (in Chinese)

       Shao JY. 2001. Measuring piconewton forces and its application in cellular and molecular biomechanics. Recent Advances in Biomechanics: Proceedings of the First International Young Investigator Workshop on Biomechanics, ed. Zhu C and M Long. CHEP Beijing and Springer-Verlag Berlin Heidelberg. 47-51.

       Shao JY. 1993. A briefing on the eighth international congress of biorheology. Bulletin of National Natural Science Foundation of China. 7:270-274. (in Chinese with English abstract)