Journal
CELL REPORTS
Volume 25, Issue 2, Pages 328-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.09.030
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Funding
- American Cancer Society [RSG-14-1-01-CSM]
- NIH [U54CA210190, R01CA181385, R01CA181385S1]
- UMN College of Science and Engineering
- Masonic Cancer Center
- UMN Institute for Engineering in Medicine
- Randy Shaver Research and Community Fund
- National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) [ECCS-1542202]
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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.
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