Cytoskeleton (Hoboken). 2016 Dec 9. doi: 10.1002/cm.21349. [Epub ahead of print]

Matrix rigidity regulates the microtubule network polarization in migration.

Raab M¹, Discher DE^1,2.

Abstract

The microtubule organizing center (MTOC) frequently polarizes to a position in front of the nucleus during cell migration, but recent work has shown conflicting evidence for the MTOC location in migratory polarized cells. Here, we show that subcellular localization of the MTOC is modulated by the extracellular matrix stiffness. Specifically, we found that ECM compliance alters the positioning of the MTOC during cell migration in scratch wound assays as well as single cell migration of mesenchymal stem cells (MSCs). In contrast to the expected polarized position in front of the nucleus, the MTOC appears randomly positioned when cells are migrating on soft matrix. The bulk of the microtubule density is also equally likely to be in front of or behind the nucleus on soft matrix, but is polarized in front of the nucleus on stiff matrix. This occurred during cell migration with cells in interphase. During cytokinesis the centrosomes polarize on either side of the chromosomes even on soft matrix, with MIIB localized in the cleavage furrow which depolarizes as cells exit cytokinesis. When cells are immobilized on micro-patterns printed on the top of substrates of different stiffness, MIIB was able to polarize if the matrix was sufficiently stiff similar to results with migrating cells. However, the MTOC was randomly positioned with respect to the nucleus independent of matrix stiffness. We deduce that cell migration is necessary to orient the MTOC in front of the nucleus and that matrix stiffness helps to drive cell polarization during migration. This article is protected by copyright. All rights reserved.