title: Thin-filament length correlates with fiber type in human skeletal muscle.
abstract: Force production in skeletal muscle is proportional to the amount of overlap between the thin and thick filaments, which, in turn, depends on their lengths. Both thin- and thick-filament lengths are precisely regulated and uniform within a myofibril. While thick-filament lengths are essentially constant across muscles and species (∼1.65 μm), thin-filament lengths are highly variable both across species and across muscles of a single species. Here, we used a high-resolution immunofluorescence and image analysis technique (distributed deconvolution) to directly test the hypothesis that thin-filament lengths vary across human muscles. Using deltoid and pectoralis major muscle biopsies, we identified thin-filament lengths that ranged from 1.19 ± 0.08 to 1.37 ± 0.04 μm, based on tropomodulin localization with respect to the Z-line. Tropomodulin localized from 0.28 to 0.47 μm further from the Z-line than the NH(2)-terminus of nebulin in the various biopsies, indicating that human thin filaments have nebulin-free, pointed-end extensions that comprise up to 34% of total thin-filament length. Furthermore, thin-filament length was negatively correlated with the percentage of type 2X myosin heavy chain within the biopsy and shorter in type 2X myosin heavy chain-positive fibers, establishing the existence of a relationship between thin-filament lengths and fiber types in human muscle. Together, these data challenge the widely held assumption that human thin-filament lengths are constant. Our results also have broad relevance to musculoskeletal modeling, surgical reattachment of muscles, and orthopedic rehabilitation.
authors.affiliation: Dept. of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Gokhin
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kim
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Lewis
authors.forename: Heinz R
authors.initials: HR
authors.lastname: Hoenecke
authors.forename: Darryl D
authors.initials: DD
authors.lastname: D'Lima
authors.forename: Velia M
authors.initials: VM
authors.lastname: Fowler
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure*; D002478:Cells, Cultured; D057645:Deltoid Muscle / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins / Q000032:analysis; D009210:Myofibrils / Q000648:ultrastructure*; D018995:Myosin Heavy Chains / Q000032:analysis*; D010369:Pectoralis Muscles / Q000502:physiology; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure*; D051348:Tropomodulin / Q000032:analysis
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D051348:Tropomodulin; C035620:nebulin; D018995:Myosin Heavy Chains
references.citation: J Cell Biol. 1994 Dec;127(6 Pt 1):1627-35
references.pmid: 7798317
references.citation: J Cell Biol. 2001 Dec 10;155(6):1043-53
references.pmid: 11739412
references.citation: Science. 1991 Mar 1;251(4997):1039-44
references.pmid: 1998120
references.citation: J Cell Biol. 2010 Apr 5;189(1):95-109
references.pmid: 20368620
references.citation: J Cell Sci. 2009 Jun 15;122(Pt 12):2119-26
references.pmid: 19470580
references.citation: J Anim Sci. 2008 Apr;86(14 Suppl):E19-35
references.pmid: 17709792
references.citation: J Biochem. 1979 May;85(5):1377-8
references.pmid: 571869
references.citation: FEBS Lett. 1991 May 6;282(2):313-6
references.pmid: 2037050
references.citation: J Cell Biol. 1991 Oct;115(1):97-107
references.pmid: 1717482
references.citation: Am J Physiol. 1991 May;260(5 Pt 1):C1060-70
references.pmid: 2035614
references.citation: Hum Mol Genet. 2011 May 15;20(10):2015-25
references.pmid: 21357678
references.citation: IEEE Trans Biomed Eng. 2007 Nov;54(11):1940-50
references.pmid: 18018689
references.citation: Muscle Nerve. 2000 Nov;23(11):1647-66
references.pmid: 11054744
references.citation: J Biol Chem. 2001 Jan 5;276(1):583-92
references.pmid: 11016930
references.citation: Adv Exp Med Biol. 1994;358:71-81
references.pmid: 7801813
references.citation: Physiol Rev. 2003 Jul;83(3):731-801
references.pmid: 12843408
references.citation: IEEE Trans Biomed Eng. 1990 Aug;37(8):757-67
references.pmid: 2210784
references.citation: Biochemistry. 1989 Oct 17;28(21):8501-6
references.pmid: 2605200
references.citation: Poult Sci. 2008 Oct;87(10):2126-32
references.pmid: 18809876
references.citation: J Cell Biol. 2010 May 31;189(5):859-70
references.pmid: 20498015
references.citation: Anat Rec. 1974 Jan;178(1):63-81
references.pmid: 4202806
references.citation: J Anim Sci. 2004 May;82(5):1445-53
references.pmid: 15144085
references.citation: J Physiol Sci. 2006 Oct;56(5):355-60
references.pmid: 17014746
references.citation: Annu Rev Cell Dev Biol. 1998;14:487-525
references.pmid: 9891791
references.citation: J Physiol. 1966 Mar;183(2):407-17
references.pmid: 5942818
references.citation: Nature. 1954 May 22;173(4412):973-6
references.pmid: 13165698
references.citation: Physiol Rev. 2008 Jan;88(1):1-35
references.pmid: 18195081
references.citation: J Mol Cell Cardiol. 1973 Aug;5(4):341-50
references.pmid: 4355337
references.citation: J Biol Chem. 1990 Dec 5;265(34):21323-9
references.pmid: 2250026
references.citation: Biophys J. 2009 Mar 4;96(5):1856-65
references.pmid: 19254544
references.citation: Prog Biophys Biophys Chem. 1957;7:255-318
references.pmid: 13485191
references.citation: J Biomech. 2011 Jan 4;44(1):109-15
references.pmid: 20889156
references.citation: Dev Dyn. 2001 May;221(1):61-71
references.pmid: 11357194
references.citation: J Cell Biol. 1993 Jan;120(2):411-20
references.pmid: 8421055
references.citation: J Appl Physiol (1985). 1994 Aug;77(2):493-501
references.pmid: 8002492
references.citation: J Cell Biol. 2006 Jun 19;173(6):905-16
references.pmid: 16769824
references.citation: Trends Cardiovasc Med. 2003 Jul;13(5):195-201
references.pmid: 12837582
references.citation: J Muscle Res Cell Motil. 1989 Jun;10(3):197-205
references.pmid: 2547831
references.citation: Nature. 1995 Sep 7;377(6544):83-6
references.pmid: 7544875
references.citation: Am J Physiol Cell Physiol. 2006 Feb;290(2):C626-37
references.pmid: 16207790
references.citation: J Biol Chem. 2010 Oct 22;285(43):33265-33280
references.pmid: 20650902
references.citation: Hum Mol Genet. 2009 Jul 1;18(13):2359-69
references.pmid: 19346529
references.citation: J Hand Surg Am. 2008 Nov;33(9):1655-6
references.pmid: 18984353
references.citation: Nat Cell Biol. 2001 Jun;3(6):544-51
references.pmid: 11389438
references.citation: J Cell Biol. 1963 Nov;19:369-90
references.pmid: 14086763
references.citation: J Physiol. 1966 May;184(1):170-92
references.pmid: 5921536
references.citation: Biophys J. 2002 May;82(5):2548-64
references.pmid: 11964243
references.citation: Semin Cell Dev Biol. 2008 Dec;19(6):511-9
references.pmid: 18793739
references.citation: J Biol Chem. 1999 Oct 1;274(40):28466-75
references.pmid: 10497209
references.citation: J Neurophysiol. 1994 Mar;71(3):874-81
references.pmid: 8201427
references.citation: J Physiol. 1966 May;184(1):143-69
references.pmid: 5921535
references.citation: Physiol Rev. 2009 Oct;89(4):1217-67
references.pmid: 19789381
references.citation: J Mol Biol. 2008 Jan 11;375(2):325-30
references.pmid: 18021803
references.citation: J Mol Biol. 2008 Dec 5;384(1):60-72
references.pmid: 18817784
references.citation: Am J Physiol. 1994 Dec;267(6 Pt 1):C1723-8
references.pmid: 7545970
references.citation: Cell Struct Funct. 1997 Feb;22(1):83-93
references.pmid: 9113394
references.citation: J Muscle Res Cell Motil. 1993 Apr;14(2):167-72
references.pmid: 8315020
references.citation: J Cell Biol. 2003 Dec 8;163(5):1033-44
references.pmid: 14657235
references.citation: Am J Physiol Cell Physiol. 2009 May;296(5):C1123-32
references.pmid: 19295172