Non-muscle myosin IIB is critical for nuclear translocation during 3D invasion.
Non-muscle myosin II (NMII) is reported to play multiple roles during cell migration and invasion. However, the exact biophysical roles of different NMII isoforms during these processes remain poorly understood. We analyzed the contributions of NMIIA and NMIIB in three-dimensional (3D) migration and in generating the forces required for efficient invasion by mammary gland carcinoma cells. Using traction force microscopy and microfluidic invasion devices, we demonstrated that NMIIA is critical for generating force during active protrusion, and NMIIB plays a major role in applying force on the nucleus to facilitate nuclear translocation through tight spaces. We further demonstrate that the nuclear membrane protein nesprin-2 is a possible linker coupling NMIIB-based force generation to nuclear translocation. Together, these data reveal a central biophysical role for NMIIB in nuclear translocation during 3D invasive migration, a result with relevance not only to cancer metastasis but for 3D migration in other settings such as embryonic cell migration and wound healing.
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 441195 Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195 egelhot@ccf.org.
Dustin G
DG
Thomas
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 441195.
Aishwarya
A
Yenepalli
Department of Biomedical Engineering, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.
Celine Marie
CM
Denais
Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720.
Andrew
A
Rape
Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Jordan R
JR
Beach
Department of Biomedical Engineering, Carnegie Melon University, Pittsburgh, PA 15219.
Yu-Li
YL
Wang
General Medical Sciences-Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106.
William P
WP
Schiemann
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106.
Harihara
H
Baskaran
Department of Biomedical Engineering, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.
Jan
J
Lammerding
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 441195 Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195 egelhot@ccf.org.
Thomas T
TT
Egelhoff
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001696:Biomechanical Phenomena; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485903:Syne2 protein, mouse; D024501:Nonmuscle Myosin Type IIB