Nuclear positioning facilitates amoeboid migration along the path of least resistance

Jörg Renkawitz, Aglaja Kopf, Julian Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, Erik S. Welf, Gaudenz Danuser, Reto Fiolka, Michael Sixt

Research output: Contribution to journalLetter

11 Citations (Scopus)

Abstract

During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments 1–3 . These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell 4,5 . Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis 6 . By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion 7 , raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.

Original languageEnglish (US)
JournalNature
DOIs
StatePublished - Jan 1 2019

Fingerprint

Microtubule-Organizing Center
Locomotion
Microtubules
Leukocytes
Proteolysis
Cues
Extracellular Matrix
Epithelial Cells
Neoplasms
Discrimination (Psychology)

ASJC Scopus subject areas

  • General

Cite this

Nuclear positioning facilitates amoeboid migration along the path of least resistance. / Renkawitz, Jörg; Kopf, Aglaja; Stopp, Julian; de Vries, Ingrid; Driscoll, Meghan K.; Merrin, Jack; Hauschild, Robert; Welf, Erik S.; Danuser, Gaudenz; Fiolka, Reto; Sixt, Michael.

In: Nature, 01.01.2019.

Research output: Contribution to journalLetter

Renkawitz, Jörg ; Kopf, Aglaja ; Stopp, Julian ; de Vries, Ingrid ; Driscoll, Meghan K. ; Merrin, Jack ; Hauschild, Robert ; Welf, Erik S. ; Danuser, Gaudenz ; Fiolka, Reto ; Sixt, Michael. / Nuclear positioning facilitates amoeboid migration along the path of least resistance. In: Nature. 2019.
@article{80441c20a7d649cca13a58010d5c17dc,
title = "Nuclear positioning facilitates amoeboid migration along the path of least resistance",
abstract = "During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments 1–3 . These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell 4,5 . Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis 6 . By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion 7 , raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.",
author = "J{\"o}rg Renkawitz and Aglaja Kopf and Julian Stopp and {de Vries}, Ingrid and Driscoll, {Meghan K.} and Jack Merrin and Robert Hauschild and Welf, {Erik S.} and Gaudenz Danuser and Reto Fiolka and Michael Sixt",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41586-019-1087-5",
language = "English (US)",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Nuclear positioning facilitates amoeboid migration along the path of least resistance

AU - Renkawitz, Jörg

AU - Kopf, Aglaja

AU - Stopp, Julian

AU - de Vries, Ingrid

AU - Driscoll, Meghan K.

AU - Merrin, Jack

AU - Hauschild, Robert

AU - Welf, Erik S.

AU - Danuser, Gaudenz

AU - Fiolka, Reto

AU - Sixt, Michael

PY - 2019/1/1

Y1 - 2019/1/1

N2 - During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments 1–3 . These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell 4,5 . Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis 6 . By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion 7 , raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.

AB - During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments 1–3 . These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell 4,5 . Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis 6 . By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion 7 , raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.

UR - http://www.scopus.com/inward/record.url?scp=85063938496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063938496&partnerID=8YFLogxK

U2 - 10.1038/s41586-019-1087-5

DO - 10.1038/s41586-019-1087-5

M3 - Letter

C2 - 30944468

AN - SCOPUS:85063938496

JO - Nature

JF - Nature

SN - 0028-0836

ER -