Huxley and Hanson's Papers on Muscle Contraction in Nature (1954), Study notes of Physiology

Download Huxley and Hanson's Papers on Muscle Contraction in Nature (1954) and more Study notes Physiology in PDF only on Docsity! JB Review J. Biochem. 117, 1-6 (1995) Birth of the Sliding Filament Concept in Muscle Contraction Koscak Maruyama Office of the President, Chiba University, Inage-ku, Chiba 263 Received for publication, September 12, 1994 Why were the two classical papers by A.F. Huxley and R. Niedergerke and by H.E. Huxley and J. Hanson on the sliding filament concept in muscle contraction published in the same issue (May 22, 1954) of Nature? This historical survey reveals the background of the two groups' monumental work. Key words: Andrew Huxley, Hugh Huxley, Jean Hanson, muscle contraction, Rolf Niedergerke, sliding filament concept. In the 1954 May 22 issue of Nature, two classical papers appeared: "Structural changes in muscle during contrac tion" by A.F. Huxley and R. Niedergerke (1) and "Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation" by H.E. Huxley and J. Hanson (2). It is generally accepted that these two short papers presented the first evidence for the sliding filament concept in muscle contraction (3, 4). By that time it was a prevailing opinion under the influence of English biophysicist William Astbury (1898- 1961) and Swiss chemist Kurt H. Meyer (1883-1953) that muscle contracted as a consequence of conformational changes of the filamentous proteins (5). For example, wide-angle X-ray diffraction work by Astbury and Dickin son had suggested that the changes of the structures of muscle contractile proteins from the ƒÀ form (ƒÀ sheet) to the a form (a helix) occurred during muscle contraction (6), although this change was later denied by Astbury himself in 1947 (7). Morales presented a primitive type of the sliding concept in 1948 (8). The sliding filament concept was revolutionary at the time, and is now regarded as a major universal mechanism of biomotility, not only in myosin/actin-based motility but also in the kinesin, dynein/microtubule-based motility of cells. A molecular motor (myosin, kinesin, and dynein) slides along a rail (actin filament or microtubule) in a definite direction dictated by the polarity of the rail, utilizing the energy derived from the splitting of ATP (Fig. la). When the motors are appropriately immobilized, then the rail is moved in a definite direction leading to the changes in length of the muscle filaments (sarcomere length) (Fig. lb). One can regard this sliding filament concept as a paradigm in biological sciences as Thomas Kuhn has defined. This article is mainly concerned with the events leading to the simultaneous publication of the two Nature papers. Attention will be especially directed to the roles played by both Huxleys and Hanson, and to their mutual relationship at that time. The Huxley-Niedergerke work Andrew Fielding Huxley, born at Hampstead, London, in 1917, was educated as a physiologist at Trinity College, Cambridge, and was an assistant director of research at the Department of Physiology, Cambridge, from 1951 to 1959. In 1951 he changed his research subject from nerve to muscle after completing the monumental papers with Alan Hodgkin on the excitation mechanism of squid giant axon (Nobel Prize for Physiology or Medicine, 1963) (10, 11). Huxley had become interested in the structure and function of striated muscle through the stimulating lectures of David Hill, a muscle physiologist [son of a great muscle physiolo gist, Archibald V. Hill (1886-1977), Nobel laureate (1922)], while he was asked to take over Hill's lectures in 1948 (10). Huxley started his muscle work by developing a new interference microscope suitable for the observation of striation changes during muscle contraction. Assisted by the firm of R. & J. Beck, he undertook to construct a high-power interference microscope, and his hand-made microscope was successfully in use (12) by the end of 1952 (10). In the autumn of 1952, Rolf Niedergerke, born at Mulheim-Ruhr, Germany, in 1921, joined Huxley's labora tory (13). He had worked on isolated nerve fibers in Alexander von Muralt's Institute in Berne. Robert Stampfli, who taught Niedergerke nerve fiber dissection, recommended him to Huxley as a collaborator for isolation of single muscle fibers (13). Niedergerke had been a demonstrator in physiology at Gottingen (13). Huxley and Niedergerke quickly reached a preliminary conclusion that the A band width in a sarcomere was fairly constant during passive stretch, isometric contraction and also isotonic contraction, to a certain extent. The force was generated while the A band remainded invariant during isometric contraction. These results were obtained by early 1953 (11). However, completion of the work was delayed due to Huxley's duties as the editor of the Journal of Physiology and the secretary of the Council of Trinity College (11). Niedergerke, who had read a number of papers on the myofibrillar structure by 19th century German workers, pointed out to Huxley the idea by Wilhelm Krause (1869) (14) that the A band (width, 1.5ƒÊm) in mammalian muscle consisted of longitudinally parallel rodlets (filaments) and the rodlets did not change in length during contraction, but attracted "fluid" from the adjacent I bands. This is a prototype of the sliding concept, if "fluid" is read as Vol. 117, No. 1, 1995 1 2 K. Maruyama "filaments" distinct from the A band rodlets . Huxley carefully examined the microscopists' work and later wrote historical overviews (10, 15). A cine film taken in March 1953 first suggested to Huxley a sliding filament system (10). A single fiber, contracting in response to a slowly increasing current, showed the forma tion of the first contraction band as a narrow dense line at the middle of the A band. Huxley assumed that the A band consisted of one kind of filaments as Krause had already mentioned (14) and further that there were another kind of filaments in the I band. The latter I filaments would be separated in the A band in a sarcomere at rest length. It followed that the first contraction band would be due to the collision between opposing sets of these I filaments at the center of the A band. The second contraction band formed near the Z line on further contraction would be due to the collision of the A filaments with the Z line. Huxley had known of the presence of two kinds of muscle contractile Fig. 1. Sliding movements of myosin motor and actin rail. a, actin rail is immobilized. Myosin motor moves on actin rail to the direction of barbed (plus) end of the actin filament. b, myosin motor is immobilized. Actin rail moves to the direction of the pointed (minus) end of the actin filament. This is the case with striated muscle contraction. M, myosin; A, actin; Z, Z line; C, connectin/titin. Modified from Hayashi and Maruyama (9). Courtesy of Yukiko Ohtani. Fig. 2. A.F. Huxley and H.E. Huxley. Near Mt. Fuji, 1979. Courtesy of Mrs. Fumiko Ebashi. proteins, myosin and actin, discovered and characterized by Albert Szent-Gyorgyi and his school at Szeged (16). Furthermore, Hugh Huxley had reported the presence of two kinds of longitudinal filaments in a sarcomere based on low-angle X-ray diffraction and electron microscopic photo- graphs of rabbit psoas fibers (17, 18). He tentatively regarded the two kinds of filaments to be myosin, located in the A band, and actin, mainly located in the I band. Although the main result of the Huxley-Niedergerke paper was the constancy of the A band width of isolated frog muscle fibers during contraction and relaxation, the insight into deeper understanding of the mechanism of muscle contraction is indeed penetrating (1) : ". . . makes very attractive the hypothesis that during contraction the actin filaments are drawn into the A-bands, between the rodlets of myosin." "If a relative force between actin and myosin is generated at each of a series of points in the region of overlap in such sarcomere, then tension per filament should be proportional to the number of this zone of overlap" (19). These implications, later proved to be actually the case, are most significant, making the Huxley-Niedergerke paper distinct from a mere observation that the A band width was constant during contraction and relaxation (20). Hugh Huxley and Jean Hanson Hugh Esmor Huxley, born at Birkenhead, Cheshire, in 1924, was educated as a physicist at Christ's College, Cambridge. H.E. Huxley (HEH) is not related to A.F. Huxley (AFH) (21). HEH became interested in biophysics rather than nuclear physics. After having spent 4 years as a research student at the MRC unit of Molecular Biology at Cavendish Laboratory, working first on crystalline proteins and then on muscle, he went to Francis 0. Schmitt's (1903-) laboratory at the Massachusetts Institute of Technology (MIT), Cambridge, MA, as a Commonwealth Foundation fellow from 1952 to 1954 to continue his work on muscle. Fig. 3. Jean Hanson. King's College Archives. Courtesy of Dr. Pauline Bennett. J. Biochem. Birth of Sliding Filament Concept 5 theory. He extented his theory together with Robert Simmons in 1971(48) . The 1957 theory dealt only with the attachment and detachment of cross-bridges while the 1971 theory with Simmons dealt with what the cross-bridges might be doing while attached. He was the Jodrell Profes sor of Physiology, University College London from 1960 to 1969, then a Royal Society Research Professor (1969- 1983). He served as President of the Royal Society (1980- 1985) and was Master of Trinity College, Cambridge from 1984-1990. Sir Andrew Huxley, OM, still is active as a researcher at Cambridge. Rolf Niedergerke went to the Department of Biophysics, University College London, in 1954, becoming a reader in 1963. He continued to work on muscle, with many distin guished contributions on the calcium activation of cardiac muscle (13). Since his retirement in 1986, he has been actively engaged in research as an emeritus reader there. In April 1954 Hugh Huxley returned to England and extended his electron microscopic work at Cambridge and University College London (1956-1961). He published an elegant electron microscopic study of muscle in 1957 (4) and furthermore, showed polarity of the location of cross- bridges on the myosin filament as well as of the actin filaments in a sarcomere (49). He continued his X-ray work on muscle contraction at the MRC Laboratory of Molecular Biology, Cambridge from 1961-1987 and received a Royal Medal from the Royal Society in 1977. In 1988 he moved to Brandeis University, MA, as professor of the Rosenstiel Medical Sciences Research Center. He served as the director there (1988-1994). Jean Hanson continued her muscle research at King's College after her return from MIT. In 1963 she demon- strated double stranded structure of the actin filament with Jack Lowy (50). She was promoted to professor in 1966 and became the director of the Muscle Biophysics unit, King's College in 1970. In August 1973 she suddenly died of fulminating meningococcal septicaemia of the adrenal cortex (Waterhouse-Friederichsen Syndrome) (26, 51). Her strong enthusiasm for science and warm personality will be long remembered by those who knew her. The writer is most grateful to Sir Andrew Huxley and Professor Hugh Huxley for their helpful personal communication. He is greatly indebted to Profesessessssor John T. Edsall, the writer's supervisor in the history of science, for his warmest encouragements and reading through the manuscript. Thanks are due to Professors F.O. Schmitt, J. Lowy, A.J. Hodge, R.M. Simmons, S. Ebashi, and M. Endo for their invaluable information. He is especially indebted to Professors Simmons and Hodge and Dr. R.T. Tregear for their scrutinizing the manuscript. Thanks are also due to Professors M.F. Morales, J. Gergely, and H. Noda for their helpful comments. REFERENCES 1. Huxley, A.F. and Niedergerke, R. (1954) Structural changes in muscle during contraction. Nature 173, 147-149 2. Huxley, H.E. and Hanson, J. (1954) Changes in the cross- striations of muscle during contraction and stretch and their structural interpretation. Nature 173, 149-152 3. Huxley, A.F. (1957) Muscle structure and theories of contraction. Prog. Biophys. Biophys. Chem. 7, 255-318 4. Huxley, H.E. (1957) The double array of filaments in cross- striated muscle. J. Biophys. Biochem. Cytol. 3, 631-648 5. Needham, D.M. (1970) Machina Carnia. Cambridge University Press, New York. Early history of theories of muscle contraction is summarized in this book. 6. Astbury, W.T. and Dickinson, S. (1935) ƒ¿-ƒÀ Transformation of muscle proteins in situ. Nature 135, 765-766 7. Astbury, W.T. (1947) On the structure of biological fibers and the problem of muscle. Proc. Roy. Soc. B 134, 303-328 8. Morales, M.F. (1948) Some qualitative considerations on the mechanism of striated muscle contraction. Biochim. Biophys. Acta 2, 618-623 9. Hayashi, T. and Maruyama, K. (1975) Myosin aggregates as a requirement for contraction and a proposal to the mechanism of contraction of actomyosin systems. J. Biochem. 78, 1031-1036 10. Huxley, A.F. (1977) Looking back on muscle in The Pursuit of Nature, pp. 23-64, Cambridge University Press, New York 11. Simmons, R.M. (1992) A.F. Huxley's research on muscle in Muscle Contraction (Simmons, R.M., ed.) pp. 19-42, Cambridge University Press, New York 12. Huxley, A.F. (1954) A high-power interference microscope. J. Physiol. 125, 11-13P 13. Niedergerke, R. and Page, S. (1992) Calcium activation of heart muscle in Muscle Contraction (Simmons, R.M., ed.) pp. 83-85, Cambridge University Press, New York 14. Krause, W. (1869) Die motorischen Endplatten der querges treiften Muskelfasern, Hahn, Hannover. Cited from Ref. 10 15. Huxley, A.F. (1980) Reflections on Muscle, Princeton University Press, Princeton 16. Szent-Gyorgyi, A. (1948) Chemistry of Muscle Contraction, 1st ed., Academic Press, New York 17. Huxley, H.E. (1953) X-ray analysis and the problem of muscle. Proc. R. Soc. 141B, 59-62 18. Huxley, H.E. (1953) Electron microscope studies of the organiza tion of the filaments in striated muscle. Biochim. Biophys. Acta 12, 387-394 19. This speculation was later substantiated by experimental evi dence: Gordon, A.M., Huxley, A.F., and Julian, F.J. (1966) The variation in isometric tension with sarcomere length in verte brate muscle fibers. J. Physiol. 184, 170-192 20. Harman, J.W. (1954) Contractions of skeletal muscle myofibrils by phase microscopy. Fed. Proc. 13, 430 21. AFH's grandfather was Thomas Henry Huxley, Darwin's strongest supporter. His half-brothers were Julian and Aldous Huxley. According to the late Jean Hanson (oral communication to the writer, October, 1965 at Tokyo), British scientists of upper class origin tended not to submit Ph.D. theses. So, AFH is not a Ph.D., nor is David Hill and Hanson added that HEH and she, both from middle class, earned Ph.D. degrees. Sir Andrew Huxley replied as following (letter to the writer, October 2, 1994): "I think that the distinction was not so much a matter of `class' as a peculiarity of Oxford and Cambridge , where the Colleges award short-term research fellowships to promising young people at about the same stage in their careers as they might be taking Ph.Ds. These fellowships are few in number and are awarded on a competitive basis and their standard is therefore much higher than that of a Ph.D., so there is no point in taking a Ph.D. if one has already been awarded a Fellowship. Not only did David Hill and I had research fellowships at Trinity but so also did Alan Hodgkin and he too never took a Ph.D. I would very likely have taken a Ph.D., if it had not been for the outbreak of world war 2. The Cambridge Ph.D. did not exist in W.B. Hardy's time; I think it was introduced in the middle 1920s." Professor R.M. Simmons commented (letter to the writer, June 28, 1994) : "I have met other people from that generation without Ph .D.s who certainly would not describe themselves as upper class. I think it was rather that established academics objected to the Ph. D. on the grounds that brilliance in research can not be ex amined." On the other hand, Dr. J.T. Edsall remarked (letter to the writer, June 17, 1994): "Certainly British scientists (and scholars in other fields) were slower to adopt the Ph.D. system than the Germans or Americans. There may have been a class factor also. In the transition period, in the early 20th century, I think that upper class people in England may have been rather scornful of the Ph.D., and thought of it as a German custom, foreign to England. William Bate Hardy (1864-1934), a really great scientist who discovered the amphoteric behavior of albu- Vol. 117, No. 1, 1995 6 K. Maruyama min in 1899, never got a Ph.D., and was just Mr. Hardy, not Professor or Doctor, until he was knighted and became Sir William. That happened early in 1925, and F.G. Hopkins got a knighthood at the same time. I remember that very well , because I had started working in the Hopkins Laboratory in Cambridge, just a few months before that. People of their generation in England, I think, never took Ph.D.s." 22. Schmitt, F.O. (1990) The Never-Ceasing Search , American Ph ilosophical Society, Philadelphia 23. Bear, R.S. (1945) Small-angle x-ray diffraction studies on muscle. J. Am. Chem. Soc. 67, 1625-1626 24. Hall, C.E., Jakus, M.A., and Schmitt, F.O. (1946) An investiga tion of cross striations and myosin filaments in muscle. Biol. Bull. 90,32-49 25. The intensity changes at 1,1 and 1,0 were later shown to be due to attachment of myosin crossbridges to actin filaments, and were repeatedly worked out by HEH. cf. Huxley, H.E., Simmons, R.M., Faruqi, A.R., Kress, M., Bordas, J., and Koch, M.H.J. (1983) Changes in the x-ray reflection from contracting muscle during rapid mechanical transients and their structural implica tions. J. Mol. Biol. 169, 469-506 26. Randall, J. (1975) Emmeline Jean Hanson. Biogr. Mem. Fellows R. Soc. Lond., 21, 313-344 27. Huxley, H.E. Oral communication. July 21, 1993, at Gordon Research Conference at New Hampshire. 28. Huxley, H.E. Letter to the writer (June 30, 1994). 29. Hodge, A.J. Letter to the writer (November 17, 1993). He was a professor of biology, Caltech from 1960 to 1972. 30. Huxley, H.E. Hanson, (Emmeline) Jean (1919-1973). Diction ary of National Biography (1971-1980), pp. 377-378 31. After going back to King's College from MIT, Hanson returned to this subject. Hanson, J. (1957) The structure of the smooth muscle fibres in the body wall of the earthworm. J. Biophys. Biochem. Cytol. 3, 111-320 32. Hanson, J., Bayley, S.T., and Randall, J. (1952) The microstruc ture of the spermatozoa of the snail Viviparus. Exp. Cell Res. 3, 65-70. In this work Hanson first learned electron microscopy using a Siemens electron microscope captured in Germany after the war time and brought to London [oral communication of Hanson to the writer (October, 1965) and confirmed by Dr. J. Lowy (1994)]. 33. Hanson, H.E. (1952) Changes in the cross-striation of myofibrils during contraction induced by adenosine triphosphate. Nature, 169,530-533 34. Huxley, H.E. Letter to the writer (May 13, 1994). 35. Hodge, A.J., Huxley, H.E., and Spiro, D. (1954) Electron microscope studies on ultra thin sections of muscle. J. Exp. Med. 99,201-206 36. Hanson, J. and Huxley, H.E. (1953) Structural basis of the cross-striations in muscle. Nature 172, 530-532 37. Hasselbach, W. (1953) Elekronmikroskopische Untersuchungen an Muskelfibrillen bei totaler and partieller Extraktion des L-Myosins. Z. Naturforsch. 8b, 449-454 38. Both Huxley and Hanson did not mention S filaments after 1955 (27). The elastic filamentous protein, connectin/titin, links the myosin filaments to the Z line [cf. Maruyama, K. Connectin, an elastic protein of striated muscle. Biophys. Chem. 50, 73-85 (1994)]. When myosin is dissolved away, most connectin/titin filaments retract toward either side of the Z line but a few opposing filaments from both Z lines appear to bind each other keeping continuity of the sarcomere [cf. Maruyama, K., Ohtani, Y., Maki, S., Kawamura, Y., Benian, G., Kagawa, H., and Kimura, S. (1995) Connectin-related phenomena and biodiver sity of connectin in Calcium as Cell Signal (Maruyama, K., Nonomura, Y., and Kohama, K., eds.) Igakushoin, Tokyo, in press]. 39. Hanson, J. and Huxley, H.E. (1955) The structural basis of contraction in striated muscle. Symp. Exp. Biol. 9, 228-264 40. H.H. Weber is father of Annemarie Weber, mother of calcium research in muscle. 41. Huxley, A.F. Oral communication to the writer. July 18, 1993, at Gordon Research Conference, New Hampshire. 42. Szent-Gyorgyi, A. Oral communication to the writer, October 1969 at Nikko, Japan. 43. Cohen, C. Oral communication to the writer on September 10, 1993, at Alpbach, Austria. 44. Sheetz, M.P. and Pollard, T.D. (1983) Movement of myosin- coated fluorescent beads on actin cables in vitro. Nature, 303, 31- 35 45. Kron, S.J. and Spudich, J.A. (1986) Fluorescent actin filaments move on myosin fixed to a glass surface. Proc. Natl. Acad. Sci. USA 83,6272-6276 46. Harada, Y., Noguchi, A., Kishino, A., and Yanagida, T. (1987) Sliding movement of single actin filaments on one-headed myosin filaments. Nature 326, 805-808 47. Rayment, I. and Holden, H.M. (1994) The three-dimensional structure of a molecular motor. Trends Biochem. Sci. 19, 129-134 48. Huxley, A.F. and Simmons, R.M. (1971) Proposed mechanism of force generation in striated muscle. Nature 233, 533-538 49. Huxley, H.E. (1963) Electron microscope studies on the struc ture of natural and synthetic protein filaments from striated muscle. J. Mol. Biol. 7, 281-308 50. Hanson, J. and Lowy, J. (1963) The structure of F-actin and of actin filaments isolated from muscle. J. Mol. Biol. 6, 46-60 51. Matsubara, 1. (1992) Scientists in the Theater Streets (in Japanese), Asahi Newspaper Press, Tokyo J. Biochem.