Maneesh Arya

Maneesh defended his PhD thesis in October, 2003. He now works on the artificial gravity project for Wyle Laboratories in Texas City, TX. His webpage while at Rice is provided below:

Initiation of Platelet Thrombus Formation: Analysis Using Optical Tweezers

Optical tweezers are an extremely useful tool in the fields of cellular and molecular biology.  In the lab of Dr. Bahman Anvari, I use the optical tweezers to study intermolecular forces of various receptor-ligand interactions associated with the cardiovascular system. Thrombosis is one of the leading causes of sickness and death and is clinically more important than all of the hemorrhagic disorders combined.  Thrombi can form in any part of the cardiovascular system and appear due to some type of endothelial cell perturbation.  While the endothelial cells are involved in the initial stage of thrombus formation, the main participants in thrombogenesis are the platelets.  Platelets adhere, alter their shape, and secrete their granular contents in thrombogenesis.  Numerous receptors on the surface of the platelet interact with various ligands causing adhesion, platelet aggregation, and a change in platelet shape. The glycoprotein (GP) Ib-IX-V complex is the protein on the platelet surface that initiates thrombus formation.  GP Ib-IX-V mediates the deposition of platelets on the subendothelium in a damaged area and initiates thrombosis by binding under high shear conditions (as in regions of a damaged vessel) to a multimeric protein called von Willebrand factor (VWF) that circulates in the plasma. By quantitatively evaluating the VWF/GP Ib-IX-V bond strength using optical tweezers, we can gain new insight into the individual molecular interactions involved in thrombogenesis and eventually develop new drugs that target specific stages in the formation of thrombi.

Using our optical tweezers, I examine the intermolecular force between GP Ib-IX-V and VWF. As a model system, we use transfected Chinese hamster ovary cells that express the platelet glycoprotein receptor. In addition, we use polystyrene beads coated with VWF. In our experiments, we trap the coated bead and let the bead and the cell adhere for a certain amount of time. We then use a piezo-electric stage to detach the cell from the bead. Using Stokes's Law, we can compute the binding force between VWF and GP Ib-IX-V. We use a titanium sapphire laser tuned to a wavelength of 830 nm to minimize cellular damage. Multimers of VWF that are of average size do not normally bind platelets so we use the exogenous modulators ristocetin and botrocetin to induce VWF/GP Ib-IX-V adhesion.   Our results are very interesting because we notice that the detachment forces of the bead from the cell occur in quantal units.  Other groups, which investigate different receptor-ligand interactions using optical tweezers, also frequently observe discrete force quantities associated with the rupture of bonds. I have also examined the bindi    color(255,255,255);ng of unusually large forms of VWF to GP Ib-IX-V and the role that various amistyle="top: 0px; height: 1600px;"no acids of the platelet receptor complex play in adhesion.  In future, I plan to investigate adhesion of different mutants of GP Ib-IX-V to VWF and also determine the significance of loading rate when detaching the bead from the cell.

Research Interests: Intermolecular forces, optical tweezers, platelet adhesion
Maneesh Arya
Bead adhesion and subsequent detachment from CHO cell. (A) VWF-coated bead is optically trapped, and CHO abIX cell is moved toward towards bead. (B) Bead adheres to cell for 10 sec. (C) After increasing laser power, bead begins to detach. (D) Bead is fully detached.
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Photomedicine and Biomedical Photonics Lab
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Last Update: July, 2002