DOI: 10.1073/pnas.94.3.849. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure

Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure

10.1073/pnas.94.3.849

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.

Bibliography

Maniotis, A. J., Chen, C. S., & Ingber, D. E. (1997). Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclearâstructure. Proceedings of the National Academy of Sciences, 94(3), 849â854.

Authors 3

Andrew J. Maniotis (first)
Christopher S. Chen (additional)
Donald E. Ingber (additional)

References 39 Referenced 1,325

10.1016/0955-0674(91)90058-7
10.1083/jcb.109.1.317
10.1126/science.8171320
10.1016/0092-8674(91)90524-3
10.1073/pnas.84.1.136
10.1007/BF02620997
10.1016/0021-9290(95)00095-X
10.1091/mbc.7.1.101
10.1002/jcb.240490406
10.1126/science.451539
10.1242/jcs.104.3.613
10.1126/science.7684161
Y C Fung Biomechanics: Mechanical Properties of Living Tissues (Springer, New York, 1988). / Biomechanics: Mechanical Properties of Living Tissues by Fung Y C (1988)
10.1016/S0006-3495(89)82660-8
D A Lauffenburger, J J Linderman Receptors: Models for Binding, Trafficking, and Signaling (Oxford Univ. Press, New York, 1993). (10.1093/oso/9780195064667.001.0001) / Receptors: Models for Binding, Trafficking, and Signaling by Lauffenburger D A (1993)
10.1126/science.1145202
10.1083/jcb.98.6.1973
10.1016/0014-4827(77)90179-3
10.1006/bbrc.1993.1662
10.1146/annurev.cb.09.110193.002211
10.1146/annurev.cb.07.110191.000521
10.1146/annurev.bi.63.070194.002021
10.1016/S0006-3495(94)81014-8
10.1083/jcb.102.4.1400
Maniotis A. Bojanowski K. & Ingber D. E. (1997) J. Cell. Biochem. in press.
10.1083/jcb.116.4.977
10.1002/cm.970180107
10.1006/excr.1994.1044
L J Gibson, M F Ashby Cellular Solids: Structure and Properties (Pergamon, New York, 1988). / Cellular Solids: Structure and Properties by Gibson L J (1988)
S H Crandall, N C Dahl, T J Lardner An Introduction to the Mechanics of Solids (McGraw–Hill, New York, 1978). / An Introduction to the Mechanics of Solids by Crandall S H (1978)
10.1038/273345a0
D E Ingber, J A Madri, J D Jamieson Am J Pathol 122, 129–139 (1986). / Am J Pathol by Ingber D E (1986)
10.1006/jtbi.1996.0120
10.1242/jcs.108.6.2131
10.1083/jcb.113.1.155
10.1126/science.7667637
10.1242/jcs.103.4.1215
10.1083/jcb.111.1.1
10.1038/307363a0

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	1 year, 7 months ago (Jan. 3, 2024, 11:52 p.m.)
Indexed	4 days, 7 hours ago (Aug. 23, 2025, 12:58 a.m.)
Issued	28 years, 6 months ago (Feb. 4, 1997)
Published	28 years, 6 months ago (Feb. 4, 1997)
Published Online	28 years, 6 months ago (Feb. 4, 1997)
Published Print	28 years, 6 months ago (Feb. 4, 1997)

Funders 0

None

BibTeX

@article{Maniotis_1997, title={Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.3.849}, DOI={10.1073/pnas.94.3.849}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Maniotis, Andrew J. and Chen, Christopher S. and Ingber, Donald E.}, year={1997}, month=feb, pages={849–854} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        23
      ]
    ],
    "date-time": "2025-08-23T04:58:59Z",
    "timestamp": 1755925139350
  },
  "reference-count": 39,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "3",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1997,
        2,
        4
      ]
    ]
  },
  "abstract": "<jats:p>We report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.</jats:p>",
  "DOI": "10.1073/pnas.94.3.849",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:35:50Z",
    "timestamp": 1027694150000
  },
  "page": "849-854",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 1325,
  "title": "Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear\u2009structure",
  "prefix": "10.1073",
  "volume": "94",
  "author": [
    {
      "given": "Andrew\u2009J.",
      "family": "Maniotis",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Departments of Pathology and Surgery, Children\u2019s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Christopher\u2009S.",
      "family": "Chen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Pathology and Surgery, Children\u2019s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115"
        }
      ]
    },
    {
      "given": "Donald\u2009E.",
      "family": "Ingber",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Pathology and Surgery, Children\u2019s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        1997,
        2,
        4
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0955-0674(91)90058-7"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.109.1.317"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8171320"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(91)90524-3"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.1.136"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF02620997"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0021-9290(95)00095-X"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.7.1.101"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcb.240490406"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.451539"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.104.3.613"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7684161"
    },
    {
      "key": "e_1_3_2_13_2",
      "volume-title": "Biomechanics: Mechanical Properties of Living Tissues",
      "author": "Fung Y C",
      "year": "1988",
      "unstructured": "Y C Fung Biomechanics: Mechanical Properties of Living Tissues (Springer, New York, 1988)."
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(89)82660-8"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "crossref",
      "DOI": "10.1093/oso/9780195064667.001.0001",
      "volume-title": "Receptors: Models for Binding, Trafficking, and Signaling",
      "author": "Lauffenburger D A",
      "year": "1993",
      "unstructured": "D A Lauffenburger, J J Linderman Receptors: Models for Binding, Trafficking, and Signaling (Oxford Univ. Press, New York, 1993)."
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1145202"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.98.6.1973"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-4827(77)90179-3"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1993.1662"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cb.09.110193.002211"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.cb.07.110191.000521"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.bi.63.070194.002021"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(94)81014-8"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.102.4.1400"
    },
    {
      "key": "e_1_3_2_25_2",
      "unstructured": "Maniotis A. Bojanowski K. & Ingber D.\u2009E. (1997) J. Cell. Biochem. in press."
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.116.4.977"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/cm.970180107"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/excr.1994.1044"
    },
    {
      "key": "e_1_3_2_29_2",
      "volume-title": "Cellular Solids: Structure and Properties",
      "author": "Gibson L J",
      "year": "1988",
      "unstructured": "L J Gibson, M F Ashby Cellular Solids: Structure and Properties (Pergamon, New York, 1988)."
    },
    {
      "key": "e_1_3_2_30_2",
      "volume-title": "An Introduction to the Mechanics of Solids",
      "author": "Crandall S H",
      "year": "1978",
      "unstructured": "S H Crandall, N C Dahl, T J Lardner An Introduction to the Mechanics of Solids (McGraw\u2013Hill, New York, 1978)."
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/273345a0"
    },
    {
      "key": "e_1_3_2_32_2",
      "first-page": "129",
      "volume": "122",
      "author": "Ingber D E",
      "year": "1986",
      "unstructured": "D E Ingber, J A Madri, J D Jamieson Am J Pathol 122, 129\u2013139 (1986).",
      "journal-title": "Am J Pathol"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jtbi.1996.0120"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.108.6.2131"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.113.1.155"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7667637"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.103.4.1215"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.111.1.1"
    },
    {
      "key": "e_1_3_2_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/307363a0"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.94.3.849",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        4
      ]
    ],
    "date-time": "2024-01-04T04:52:45Z",
    "timestamp": 1704343965000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.94.3.849"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1997,
        2,
        4
      ]
    ]
  },
  "references-count": 39,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          1997,
          2,
          4
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.94.3.849"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.94.3.849",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        1997,
        2,
        4
      ]
    ]
  },
  "assertion": [
    {
      "value": "1996-07-23",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1996-11-25",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1997-02-04",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}