Electron Tomography of Muscle Sarcomere

Laboratory of Pradeep Luther, PhD



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    Luther, P.K. and S.B. Marston (2024)

Spotlight review: Complex architecture of cardiac muscle thick filaments revealed. Trends Pharmacol Sci,  45(3): 191-192.

  Morris, E.P., C. Knupp. & P.K. Luther (2023)

Obituary: Professor John Michael Squire. J Muscle Res Cell Motil 44, 125–132. DOI: 10.1007/s10974-023-09656-2

  Huang, X, I. Torre, M. Chiappi, Z. Yin, A. Vydyanath, S. Cao, O. Raschdorf, M. Beeby, B. Quigley, P. de Tombe, J. Liu, E.P. Morris, P.K. Luther (2023) 

Cryo-electron tomography of intact cardiac muscle reveals myosin binding protein-C linking myosin and actin filaments. J. Musc. Res. Cell Motility. DOI 10.1007/s10974-023-09647-3.

  Millane, R.P. and P.K. Luther. (2023)

The vertebrate muscle superlattice: discovery, consequences, and link to geometric frustration. J.Musc.Res Cell Motility. DOI: 10.1007/s10974-023-09642-8

  Millane, R. P., D. H. Wojtas, C. Hong Yoon, N. D. Blakeley, P. J. Bones, A. Goyal, J. M. Squire and P. K. Luther (2021).

"Geometric frustration in the myosin superlattice of vertebrate muscle." J Royal Society Interface 18(185): 20210585.

  Filomena, M.C., D.L. Yamamoto, M. Caremani, V.K. Kadarla, G. Mastrototaro, S. Serio, A. Vydyanath, M. Mutarelli, A. Garofalo, I. Pertici, R. Knoll, V. Nigro, P.K. Luther, R.L. Lieber, M.R. Beck, M. Linari, and M.L. Bang. (2020).

Myopalladin promotes muscle growth through modulation of the serum response factor pathway. J Cachexia Sarcopenia Muscle. 11:169-194. DOI: 10.1002/jcsm.12486

  Squire, J.M., and P.K. Luther. (2019).

Mammalian muscle fibers may be simple as well as slow. J Gen Physiol. 151:1334-1338

  Burgoyne, T., J.M. Heumann, E.P. Morris, C. Knupp, J. Liu, M.K. Reedy, K.A. Taylor, K. Wang, and P.K. Luther. (2019).

Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle. Proc Natl Acad Sci U S A. 116:15534-15539

  Barefield, D.Y., J.W. McNamara, T.L. Lynch, D.W.D. Kuster, S. Govindan, L. Haar, Y. Wang, E.N. Taylor, J.N. Lorenz, M.L. Nieman, G. Zhu, P.K. Luther, A. Varro, D. Dobrev, X. Ai, P.M.L. Janssen, D.A. Kass, W.K. Jones, R.J. Gilbert, and S. Sadayappan. (2019).

Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury. J Mol Cell Cardiol. DOI 10.1016/j.yjmcc.2019.03.006

  Toepfer, C.N., M.B. Sikkel, V. Caorsi, A. Vydyanath, I. Torre, O. Copeland, A.R. Lyon, S.B. Marston, P.K. Luther, K.T. Macleod, T.G. West, and M.A. Ferenczi. (2016).

A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation. Am J Physiol Heart Circ Physiol. 311:H465-475.


Jacob, F., A.Y. Yonis, F. Cuello, P. Luther, T. Schulze, A. Eder, T. Streichert, I. Mannhardt, M.N. Hirt, S. Schaaf, J. Stenzig, T. Force, T. Eschenhagen, and A. Hansen. (2016)

Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue. PLoS One. 11:e0145937.


  Burgoyne, T., E.P. Morris, and P.K. Luther,

 Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle. J Mol Biol, 2015.

  Luther, P. and J. Squire (2014). "The Intriguing Dual Lattices of the Myosin Filaments in Vertebrate Striated Muscles: Evolution and Advantage." Biology 3(4): 846-865.

  Hirt, M. N., Boeddinghaus, J.,Mitchell, A., Schaaf, S., Bornchen, C., Muller, C., Schulz, H., Hubner, , Stenzig, J., Stoehr, A., Neuber, C., Eder, A., Luther, P. K., Hansen, A., Eschenhagen, T. (2014). "Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation." J Mol Cell Cardiol 74: 151-161.

Squire JMGuerreiro MJSidebotham RLReis CAWiseman JLuther PK (2013) Quantitative MUC5AC and MUC6 mucin estimations in gastric mucus by a least-squares minimisation method." Anal Biochem.




Solomon A, Smyth E, Mitha N, Pitchford S, Vydyanath A, Luther PK, Thorley AJ, Tetley TD, Emerson M (2013) Induction of platelet aggregation after a direct physical interaction with diesel exhaust particles. J Thromb Haemost 11(2):325-334.



Burgoyne T, Dixon M, Luther P, Hogg C, Shoemark A (2012) Generation of a three-dimensional ultrastructural model of human respiratory cilia.  Am J Respir Cell Mol Biol 47(6):800-806.


  Vydyanath, A., C. A. Gurnett, Marston, S., Luther, P.K. (2012). "Axial distribution of myosin binding protein-C is unaffected by mutations in human cardiac and skeletal muscle." J Muscle Res Cell Motil.

  Luther, P. K. and R. Craig (2011). "Modulation of striated muscle contraction by binding of myosin binding protein C to actin." Bioarchitecture 1(6): 277-283.


Govindan, S., McElligott, A., Muthusamy, S., Nair, N., Barefield, D., Martin, J. L., Gongora, E., Greis, K. D., Luther, P. K., Winegrad, S., Henderson, K. K., Sadayappan, S.  (2011) Cardiac myosin binding protein-C: a new diagnostic role for myocardial infarction.   J. Mol Cell Card. (PubMed)

Press coverage


  Luther, P.K, Winkler, H., Taylor, K., Zoghbi, M.E., Craig, R., Padron, R., Squire, J.M. and Liu, J. (2011) Direct visualisation of myosin binding protein C bridging myosin and actin filaments in intact muscle. Proc. Nat. Academy Sciences. U S A 108(28): 11423-11428. (PubMed)

The story behind the research

  Luther, P.K. and Vydyanath, A. (2011)  Myosin binding protein-C:  An essential protein in skeletal and cardiac muscle. J. Muscle Res Cell Motility. 31:303-305

Machuca-Tzili,L.E., Thorpe, A., Timson, C.M., Wigmore, P., Luther, P.K. and Brook, D. (2011)   Deficiency of Muscleblind-like 2 Causes Myotonic Dystrophy Splicing Alterations and Developmental Abnormalities in Zebrafish Embryos.  Disease Models and Mechanisms. Doi:10.1242/dmm.004150


  Bhavsar, P.K., N.J. Brand, L.E. Felkin, P.K. Luther, M.E. Cullen, M.H. Yacoub, and P.J. Barton. (2010)  Clenbuterol induces cardiac myocyte hypertrophy via paracrine signalling and fibroblast-derived IGF-1. J Cardiovasc Transl Res. 3:688-95.

  Luther, P.K. (2009)  The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling. J Muscle Res Cell Motil. 30:171-85.


20 Aug 2011: The review is in the top 5 most downloaded papers in the Journal of Muscle Research and Cell Motility in the last 90 days.  See here


  Yoon, C.H., B. Bodvarsson, S. Klim, M. Morkebjerg, S. Mortensen, J. Chen, J.R. Maclaren, P.K. Luther, J.M. Squire, P.J. Bones, and R.P. Millane. (2009)  Determination of myosin filament orientations in electron micrographs of muscle cross sections. IEEE Trans Image Process. 18:831-9.

  Burgoyne T, Muhamad F, Luther PK. Visualization of cardiac muscle thin filaments and measurement of their lengths by electron tomography. Cardiovasc Res. 2008;77:707-712.

  Bödvarsson, B., S. Klim, M. Mørkebjerg, S. Mortensen, C.H. Yoon, J. Chen, J.R. Maclaren, P.K. Luther, J.M. Squire, P.J. Bones, and R.P. Millane. (2008)  A morphological image processing method for locating myosin filaments in muscle electron micrographs. Image and Vision Computing. 26:1073-1080.

  Luther, P.K., P.M. Bennett, C. Knupp, R. Craig, R. Padron, S.P. Harris, J. Patel, and R.L. Moss. (2008)  Understanding the organisation and role of myosin binding protein C in normal striated muscle by comparison with MyBP-C knockout cardiac muscle. J Mol Biol. 384:60-72.


Squire, J.M., Al-Khayat, H.A., Knupp, C., Luther, P.K.  (2005)  Molecular architecture in muscle contractile assemblies.  Adv Protein Chem, 71:17-87.


  Joya, J.E., Kee, A.J., Nair-Shalliker, V., Ghoddusi, M., Nguyen, M-A.T., Luther, P. & Hardeman, E.C.  (2004)  Muscle weakness in a mouse model of nemaline myopathy can be reversed with exercise and reveals a novel myofiber repair mechanism.  Human Mol. Gen. 13:2633-2645.

  Luther, P.K.  & Morris, E.P. (2003)  Cryo-electron microscopy of refrozen cryosections.   J. Struct. Biol. 142:233-240. 


Squire, J.M., Luther, P.K. & Knupp, C..  (2003) Structural evidence for the interaction of C-protein (MyBP-C) with  actin and sequence identification of a possible actin-binding domain.  J. Mol. Biol. 331:713-724.



Luther, P.K., Padron, R., Ritter, S., Craig, R. & Squire, J.M..  (2003)  Heterogeneity of Z-band structure within a single muscle sarcomere: implications for sarcomere assembly.   J. Mol. Biol. 332:161-169.



Luther, P.K., Barry, J. & Squire, J.M.  (2002)  Three-dimensional structure of a vertebrate wide (slow muscle) Z-band: Lessons on Z-band assembly. J. Mol. Biol. 315:9-19. (Journal Cover).



Luther, P.K. & Squire, J.M. (2002)  Muscle Z-band ultrastructure: Titin Z-repeats and Z-band periodicities do not match.  J. Mol. Biol. 319:1157-1164.



Cantino, M. E., Chew, M. W., Luther, P. K., Morris, E. & Squire, J. M. (2002)  Structure and nucleotide-dependent changes of thick filaments in relaxed and rigor plaice fin muscle.  J. Struct. Biol. 137:164-175. PubMed Abstract.



Knupp, C, Luther, P.K. & Squire, J.M. (2002)   Titin organisation and the 3D architecture of the vertebrate striated muscle I-band.  J. Mol. Biol. 322:731-739.


Knupp C., Munro P.M.G., Luther PK., Ezra E., & Squire JM (2000)  Structure of abnormal molecular assemblies (collagen VI) associated with human full thickness macular holes. J. Struct. Biol., 129:38-47.


    Luther, P.K. (2000)   Three-dimensional structure of a vertebrate muscle Z-band: Implications for titin and a-actinin binding. J. Struct. Biol., 129:1-16.
    Cantino, M.E., Brown, L.D., Chew, M., Luther, P.K. & Squire, J.M. (2000)  A-band architecture in vertebrate skeletal muscle: polarity of the myosin head array.  J. Muscle Research & Cell Motility, 21:681-690.
    Knupp. C, Luther, P.K., Morris, E.P., Knight, D.P. & Squire, J.M. (1999)  Partially systematic molecular packing in the hexagonal columnar phase of dogfish egg case collagen.  J. Struct. Biol 126:121-130.
    Squire, J., Cantino, M., Chew, M., Denny, R., Harford, J., Hudson, L. & Luther, P. (1998)  Myosin rod-packing schemes in vertebrate muscle thick filaments.  J. Struct. Biol., 122:128-138.




Harford J., Cantino M., Chew M., Denny R., Hudson L., Luther P., Mendelson R., Morris E. & Squire J.  (1998)  Myosin crossbridge configurations in equilibrium states of vertebrate skeletal muscle.  Heads swing axially or turn upside-down between resting and rigor.  Adv. in Exp. Medicine & Biology. 453:297-308.



Luther, P.K., Squire, J.M. & Forey, P.L.  (1996)  Evolution of the simple lattice and superlattice A-band in vertebrate skeletal muscle.  J. Morphology, 229:329-335.

    Luther, P.K. Munro, P.M.G. & Squire, J.M. (1995)  Muscle ultrastructure in the teleost fish. Micron,   26:431-459.

Luther, P.K.  (1995)  Symmetry of vertebrate muscle basketweave Z-band.  J. Structural Biology, 115:275-282.


Serpell, L.C., Sunde, M., Fraser, P.E., Luther, P.K., Morris, E., & Blake, C.C.F. (1995)  The examination of the structure of the transthyretin amyloid fibril by image reconstruction from electron micrographs.  J. Molec. Biol. 254:113-118.

    Harford, J., Luther, P. & Squire, J. (1994)  Equatorial A-band and I-band X-ray diffraction from relaxed and active fish muscle: further details of myosin crossbridge behaviour.  J. Mol. Biol. 239:500-512.
    Pask, H.T., Jones, K.L., Luther, P.K. & Squire, J.M. (1994)  M-band structure, M-bridge interactions and contraction speed in vertebrate cardiac muscles.  J. Muscle Res. Cell Motility, 15:633-645.

  Luther, P.K. "Three-dimensional reconstruction of a simple Z-band in fish muscle" (1991) J. Cell Biol. 113:1043-1055. (Cover picture)
    Sjostrom, M., Squire, M.J., Luther, P., Morris E. and Edman, A-C. (1991)  Cryoultramicrotomy of muscle: improved preservation and resolution of muscle ultrastructure using negatively stained ultrathin cryosections.  J. Microscopy, 163:29-42.

  Luther, P.K., Lawrence, M. and Crowther, R.A. (1988)  A method for monitoring the collapse of plastic sections in the electron microscope.  Ultramicroscopy, 24, 7-18.  (Cover picture)

Squire, J.M., Luther, P.K. and Agnew, G.D. (1986)  Averaging of periodic images using a microcomputer.  J.Microsc. 142:289-300.


    Luther, P.K. & Crowther, R.A. (1984)  Three-dimensional reconstruction from tilted sections of fish muscle M-band.  Nature, 307:566-568.
    Crowther, R.A. and Luther, P.K. (1984)  Three-dimensional reconstruction from a single oblique section of fish muscle M-band.  Nature, 307:569-570.
    Holt, D.B., Lesniak, P. and Luther, P. (1983)  Image processing of SEM micrographs of integrated circuits for defect location.  J. Mat. Sci. Letters, 2:565‑569.
    Luther, P.K., Munro, P.M.G. and Squire, J.M. (1981)  Three-dimensional structure of the vertebrate muscle A-band. III. M-region structure and myosin filament symmetry.  J.Mol.Biol. 151:703-730.
    Freundlich, A., Luther, P.K. and Squire, J.M. (1980)   High‑voltage electron microscopy of crossbridge interactions in striated muscle.  J. Muscle Res. Cell Motility, 1: 321‑343.
    Luther, P.K. and Squire, J.M. (1980)  Three-dimensional structure of the vertebrate muscle A-band. II. The myosin filament superlattice.  J.Mol.Biol. 141: 409-439.


Luther, P.K. and Squire, J.M. (1978)  Three-dimensional structure of the vertebrate muscle M-region.  J.Mol.Biol. 125:313-324. 




Book Chapters and Reviews

Squire, J.M., C. Knupp, and P.K. Luther. 2008. Zebrafish - topical, transparent, and tractable for ultrastructural studies. J Gen Physiol. 131:439-43.

Luther, P.K. (2007)   Structural analysis of cardiac muscle by modern electron microscopy.  British Society for Cardiovascular Research Bulletin, 20:4-10.

Luther, P.K. (2007)   Sample shrinkage and radiation damage of plastic sections, in “Electron Tomography, Second Edition” (ed. J. Frank) Springer, New York, 17-48.

Luther, P.K. (2004) Evolution of the Muscle Lattice in the Vertebrate Kingdom, Microscopy and Analysis, March 2004.

Luther, P.K. (2001)  Section shrinkage: Impact for routine and 3D electron microscopy, Microscopy and Analysis, 7-9.

Harford, J., Cantino, M., Chew, M., Denny, R., Hudson, L., Luther, P., Mendelson, R., Morris, E. & Squire, J. (1998)  Myosin crossbridge configurations in equilibrium states of vertebrate skeletal muscle.  In “Mechanisms of work production and work absorption in muscle”, eds Sugi & Pollack. Plenum Press.

Luther, P.K. (1992)  Section shrinkage and radiation damage, in "Electron Tomography" (ed. J. Frank) Plenum, New York, 39-60.  

Squire, J.M., Morris, E.P. & Luther, P.K. (1990)  Organisation and Properties of the striated Muscle Sarcomere.  In "Molecular Mechanisms in Muscular Contraction" ed. J. Squire 1-48. "Topics in Molecular and Structural Biology" (series editors Neidle & Fuller) Macmillan.

Crowther, R.A., Luther, P.K. and Taylor, K.A. (1990)  Computation of a three dimensional image of a periodic specimen from a single view of an oblique section.  Electron Microscopy Rev. 3, 29-42. 

Seymour, J. and Luther, P.K. (1987)  Three-dimensional image processing methods for electron micrographs.  In “Fibrous Protein Structure and Function” (eds. Squire, J.M. and Vibert, P.J.) Academic Press, London. 

Squire, J.M., Luther, P.K. and Trinick, J. (1987)  Muscle myofibril architecture.  In "Fibrous Protein Structure and Function" (eds. Squire, J.M. and Vibert, P.J.) Academic Press, London.