Microtubule-Actomyosin Mechanical Cooperation During Contact Guidance Sensing

Erdem D. Tabdanov, Vikram Puram, Alexander Zhovmer, Paolo P. Provenzano
Paolo P. Provenzano, University of Minnesota

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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: Contact guidance, Carcinoma metastasis, Microtubules

Materials & Methods: Refer to paper.

Cell Type(s): Cancer Cells, Human Breast Carcinoma