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Force measurements on cargoes in living cells reveal collective dynamics of microtubule motors.

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Title: Force measurements on cargoes in living cells reveal collective dynamics of microtubule motors.
Authors: Hendricks, Adam G.1, Holzbaur, Erika L. F.1, Goldman, Yale E.1 goldmany@mail.med.upenn.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 11/6/2012, Vol. 109 Issue 45, p18447-18452. 6p.
Subjects: Microtubules, Molecular motor proteins, Organelles, Cytoplasm, Cytoplasmic filaments
Abstract: Many cellular cargoes move bidirectionally along microtubules, driven by teams of plus- and minus-end-directed motor proteins. To probe the forces exerted on cargoes during intracellular transport, we examined latex beads phagocytosed into living mammalian macrophages. These latex bead compartments (LBCs) are encased in membrane and transported along the cytoskeleton by a complement of endogenous kinesin-1, kinesin-2, and dynein motors. The size and refractive index of LBCs makes them well-suited for manipulation with an optical trap. We developed methods that provide in situ calibration of the optical trap in the complex cellular environment, taking into account any variations among cargoes and local viscoelastic properties of the cytoplasm. We found that centrally and peripherally directed forces exerted on LBCs are of similar magnitude, with maximum forces of ∼20 pN. During force events greater than 10 pN, we often observe 8-nm steps in both directions, indicating that the stepping of multiple motors is correlated. These observations suggest bidirectional transport of LBCs is driven by opposing teams of stably bound motors that operate near force balance. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 83515379
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  Data: Force measurements on cargoes in living cells reveal collective dynamics of microtubule motors.
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  Data: <searchLink fieldCode="AR" term="%22Hendricks%2C+Adam+G%2E%22">Hendricks, Adam G.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Holzbaur%2C+Erika+L%2E+F%2E%22">Holzbaur, Erika L. F.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Goldman%2C+Yale+E%2E%22">Goldman, Yale E.</searchLink><relatesTo>1</relatesTo><i> goldmany@mail.med.upenn.edu</i>
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  Data: <searchLink fieldCode="DE" term="%22Microtubules%22">Microtubules</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+motor+proteins%22">Molecular motor proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Organelles%22">Organelles</searchLink><br /><searchLink fieldCode="DE" term="%22Cytoplasm%22">Cytoplasm</searchLink><br /><searchLink fieldCode="DE" term="%22Cytoplasmic+filaments%22">Cytoplasmic filaments</searchLink>
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  Data: Many cellular cargoes move bidirectionally along microtubules, driven by teams of plus- and minus-end-directed motor proteins. To probe the forces exerted on cargoes during intracellular transport, we examined latex beads phagocytosed into living mammalian macrophages. These latex bead compartments (LBCs) are encased in membrane and transported along the cytoskeleton by a complement of endogenous kinesin-1, kinesin-2, and dynein motors. The size and refractive index of LBCs makes them well-suited for manipulation with an optical trap. We developed methods that provide in situ calibration of the optical trap in the complex cellular environment, taking into account any variations among cargoes and local viscoelastic properties of the cytoplasm. We found that centrally and peripherally directed forces exerted on LBCs are of similar magnitude, with maximum forces of ∼20 pN. During force events greater than 10 pN, we often observe 8-nm steps in both directions, indicating that the stepping of multiple motors is correlated. These observations suggest bidirectional transport of LBCs is driven by opposing teams of stably bound motors that operate near force balance. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1073/pnas.1215462109
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      – Code: eng
        Text: English
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        PageCount: 6
        StartPage: 18447
    Subjects:
      – SubjectFull: Microtubules
        Type: general
      – SubjectFull: Molecular motor proteins
        Type: general
      – SubjectFull: Organelles
        Type: general
      – SubjectFull: Cytoplasm
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      – SubjectFull: Cytoplasmic filaments
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      – TitleFull: Force measurements on cargoes in living cells reveal collective dynamics of microtubule motors.
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              M: 11
              Text: 11/6/2012
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              Y: 2012
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