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Structures of FN-III-1

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Movies of stretching FN-III-1:
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Tissues of the human body are composed of specialized cells held together by a connective fabric of proteins, that form the knots of a net glueing cells together. Upon stretching tissues, the knots unravel, rendering the net larger, but mysteriously also firmer. A protein called fibronectin-III-1 plays a particularly important role in the latter respect. Atomic force microscopy revealed that under mechanical tension fibronectin-III-1 stretches to ten times its initial length; but is does so in two steps, the first stretching step leading to net strengthening. It had been discovered earlier that other fibronectins found between cells are made of two sheets packed like a sandwich, but the structure of fibronectin-III-1 remained elusive. In an experimental-computational collaboration reported recently, the structure has now been resolved that at first sight looked similar to the sandwich structure of the other fibronectins, but on closer inspection showed a weak and a strong sheet. Simulations using NAMD revealed that stretching of the protein unravels readily the weak sheet, and only therafter the strong sheet. It turns out that the strong sheet of fibronectin-III-1 by itself, known as anastellin, inhibits tumor growth. Stretching of fibronectin-III-1, as it occurs naturally in tissue, unravels apparently half of the protein to render it extremely adhesive, strengthening a protein net that prevents metastasis of cancer cells and also assists wound healing (press release, more).