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Microtubule-Actomyosin Mechanical Cooperation during Contact Guidance Sensing.

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.

SUBMITTER: Tabdanov ED

PROVIDER: S-EPMC6226003 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Microtubule-Actomyosin Mechanical Cooperation during Contact Guidance Sensing.

Tabdanov Erdem D ED Puram Vikram V Zhovmer Alexander A Provenzano Paolo P PP

Cell reports 20181001 2

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-microtu ...[more]

PMID: 30304674

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