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Mechanical Durotactic Environment Enhances Specific Glioblastoma Cell Responses

1
National Research Council-Nanotechnology Institute, 73100 Lecce, Italy
2
National Research Council-Nanotechnology Institute, 00185 Rome, Italy
3
Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy
4
National Research Council-Institute for Microelectronics and Microsystems, via del Fosso del Cavaliere 100, 00133 Roma, Italy
5
Center for Life Nanoscience, Istituto Italiano di Tecnologia, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 643; https://doi.org/10.3390/cancers11050643
Received: 28 March 2019 / Revised: 17 April 2019 / Accepted: 7 May 2019 / Published: 9 May 2019
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Abstract

Background: A hallmark of glioblastoma is represented by their ability to widely disperse throughout the brain parenchyma. The importance of developing new anti-migratory targets is critical to reduce recurrence and improve therapeutic efficacy. Methods: Polydimethylsiloxane substrates, either mechanically uniform or presenting durotactic cues, were fabricated to assess GBM cell morphological and dynamical response with and without pharmacological inhibition of NNMII contractility, of its upstream regulator ROCK and actin polymerization. Results: Glioma cells mechanotactic efficiency varied depending on the rigidity compliance of substrates. Morphologically, glioma cells on highly rigid and soft bulk substrates displayed bigger and elongated aggregates whereas on durotactic substrates the same cells were homogeneously dispersed with a less elongated morphology. The durotactic cues also induced a motility change, cell phenotype dependent, and with cells being more invasive on stiffer substrates. Pharmacological inhibition of myosin or ROCK revealed a rigidity-insensitivity, unlike inhibition of microfilament contraction and polymerization of F-actin, suggesting that alternative signalling is used to respond to durotactic cues. Conclusions: The presence of a distinct mechanical cue is an important factor in cell migration. Together, our results provide support for a durotactic role of glioma cells that acts through actomyosin contractility to regulate the aggressive properties of GBM cells. View Full-Text
Keywords: glioblastoma; cell movement; cellular microenvironment; mechanotaxis glioblastoma; cell movement; cellular microenvironment; mechanotaxis
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Palamà, I.E.; D’Amone, S.; Ratano, P.; Donatelli, A.; Liscio, A.; Antonacci, G.; Testini, M.; Di Angelantonio, S.; Ragozzino, D.; Cortese, B. Mechanical Durotactic Environment Enhances Specific Glioblastoma Cell Responses. Cancers 2019, 11, 643.

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