Pursuing the middleman : the hunt for integrins

By the mid-1970s, the idea of a transmembrane molecule linking the cytoskeleton to the extracellular matrix (ECM) had some supporting evidence. Adhesion molecules were hot in areas ranging from developmental biology to tumor biology, and the mounting suggestive evidence that a “fibronectin receptor” existed made it a “Holy Grail” for the next decade, recalls Richard Hynes, discoverer of fibronectin, in a memoir (Hynes, 2004).

Alan “Rick” Horwitz, then at the University of Pennsylvania in Philadelphia, had joined the gaggle of labs using antibodies to look for important cell adhesion players. But he was intimidated by the tedious, iterative method of the day in which labs generated polyclonal antibodies to cell surface molecules, screened them for the ability to disrupt adhesion, and then tried to narrow down antigens by successive purification and new antibody generation.

Not only did...