Protein molecules are made up of a linear chain of amino acids that folds into a 3-D globular form. Discovering the manner and conditions under which sections of a protein molecule unravel to reveal active sites is fundamental to understanding many biochemical processes, since these are potential binding sites for other molecules.
Only recently, with the development of ultrasensitive instruments such as atomic force microscopy (AFM) and laser tweezers, have scientists been able to measure the tensile forces required to induce chain unraveling of a single molecule, and determine the strength and stability of the bonds formed with other proteins.
Xiaohui “Frank” Zhang, an assistant professor in the bioengineering program and department of mechanical engineering and mechanics, was part of the Harvard Medical School research group that first measured the force required to unravel a single von Willebrand factor molecule—the protein that initiates blood clotting—using laser tweezers. Their work was published last year in Science.
In a study published in Nature in 2010, they found that, depending on external forces, two different bonding states could exist between a protein and the surface of a blood platelet. A bond formed at shear forces above 10 pN had a lifetime 20 times longer than a bond formed at lower shear forces.
At Lehigh, Zhang is studying integrins, a family of proteins that play significant roles in cardiovascular diseases. Using laser tweezers and AFM-based techniques, he is examining the influence of drugs and intracellular activation signals on the 3-D structure and activation states of these molecules.
