Microtubule-Actomyosin Mechanical Cooperation during Contact Guidance Sensing

Erdem D Tabdanov; Vikram Puram; Alexander Zhovmer; Paolo P Provenzano

doi:10.1016/j.celrep.2018.09.030

Microtubule-Actomyosin Mechanical Cooperation during Contact Guidance Sensing

Cell Rep. 2018 Oct 9;25(2):328-338.e5. doi: 10.1016/j.celrep.2018.09.030.

Authors

Erdem D Tabdanov¹, Vikram Puram², Alexander Zhovmer³, Paolo P Provenzano⁴

Affiliations

¹ Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA; University of Minnesota Physical Sciences in Oncology Center, Minneapolis, MN 55455, USA. Electronic address: [email protected].
² Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA; University of Minnesota Physical Sciences in Oncology Center, Minneapolis, MN 55455, USA.
³ NIH, Bethesda, MD 20892, USA.
⁴ Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA; University of Minnesota Physical Sciences in Oncology Center, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Engineering in Medicine, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: [email protected].

Abstract

Cancer cell migration through and away from tumors is driven in part by migration along aligned extracellular matrix, a process known as contact guidance (CG). To concurrently study the influence of architectural and mechanical regulators of CG sensing, we developed a set of CG platforms. Using flat and nanotextured substrates with variable architectures and stiffness, we show that CG sensing is regulated by substrate stiffness and define a mechanical role for microtubules and actomyosin-microtubule interactions during CG sensing. Furthermore, we show that Arp2/3-dependent lamellipodia dynamics can compete with aligned protrusions to diminish the CG response and define Arp2/3- and Formins-dependent actin architectures that regulate microtubule-dependent protrusions, which promote the CG response. Thus, our work represents a comprehensive examination of the physical mechanisms influencing CG sensing.

Keywords: carcinoma metastasis; contact guidance; microtubules.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Actin Cytoskeleton / metabolism
Actomyosin / metabolism*
Breast Neoplasms / physiopathology*
Cell Adhesion*
Cell Communication*
Cell Movement*
Extracellular Matrix / metabolism*
Female
Humans
Microtubules / metabolism*
Pseudopodia / physiology
Tumor Cells, Cultured

Substances

Actomyosin

Abstract

Publication types

MeSH terms

Substances

Grants and funding