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Eur. J. Biochem. 271, 1403–1415 (2004) Ó FEBS 2004



Fifty years of muscle and the sliding filament hypothesis
Hugh E. Huxley
Rosenstiel Center, Brandeis University, Waltham, MA, USA

This review describes the early beginnings of X-ray diffraction work on muscle structure and the contraction mechanism in the MRC Unit in the CavendishLaboratory, Cambridge, and later work in the MRC Molecular Biology Laboratory in Hills Road, Cambridge, where the author worked for many years, and elsewhere. The work has depended heavily on instrumentation development, for which the MRC laboratory had made excellent provision. The search for ever higher X-ray intensity for time-resolved studies led to the development of synchrotron radiation as anexceptionally powerful X-ray source. This led to the first

direct evidence for cross-bridge tilting during force generation in muscle. Further improvements in technology have made it possible to study the fine structure of some of the X-ray reflections from contracting muscle during mechanical transients, and these are currently providing remarkable insights into the detailed mechanism of forcedevelopment by myosin cross-bridges. Keywords: muscle; structure; contraction; X-ray diffraction; synchrotron radiation; MRC Laboratory of Molecular Biology.

Early days at the MRC (1948–1952)
I came to the MRC Laboratory as a research student in the summer of 1948, when it was called the MRC Unit for Work on the Molecular Structure of Biological Systems, and consisted of Max Perutz and JohnKendrew, who became my supervisor. Francis Crick joined the unit a short time later, and Jim Watson was there during my last year as a graduate student. I had just finished Part II Physics in 1948, in my third year in Cambridge, a degree interrupted by four years of working on radar development in the RAF, during the war. Though extremely ignorant of biology, I had picked up the idea that there mightbe interesting applications of physics to biological and medical problems. Joining the MRC Unit sounded like a good way of following that line, with the advantage that I could stay on and perform research in Cambridge. This had been my ambition for many years, though in a different field. I had just finished learning all about the remarkable ways in which the physical properties of matter –mechanical, thermal, electrical – could be accounted for by the properties and interaction of atoms, which depended on atomic structure. So it seemed obvious that now one needed to find out about the structure of biological systems, at the atomic and molecular levels, to understand how they worked. X-ray diffraction seemed to offer a way of doing just that, which this group was exploring, but of course Ihad no way of knowing just how extraordinarily fortunate I was to join them. Nor did we ever dream of quite how important those years would turn out to be.

Correspondence to H. E. Huxley, Brandeis University, Mailstop 029, 415 South Street, MA 02454-9110, USA. (Received 31 October 2003, accepted 18 February 2004)

I did recognize that I was quite fortunate, as Max, John and Francis were allsuch marvelous people to be with, and I admired and liked them very much. They created a lighthearted, stimulating intellectual environment, with high standards and ambitious objectives. It was so exhilarating to be back again in Cambridge, now as a research student, very soon after the end of World War II. The clouds of the 1930s had gone, we had won the war against Fascism – and many of us hadhelped to do so – and now there were all sorts of marvelous ideas and research flourishing around us – Hoyle, Bondi and Gold with their theory of continuous creation, Fred Sanger sequencing insulin, Martin Ryle doing great things in radio astronomy, the first EDSAC computer whirring away in the maths lab, Nikolaus Pevsner lecturing on Renaissance Art and Architecture in Italy – and great hopes for the...
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