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J Cell Sci. 2018 May 29;131(10). pii: jcs212886. doi: 10.1242/jcs.212886.

Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing.

Author information

1
Ludwig-Maximilians-University Munich, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany.
2
ibidi GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany.
3
Ludwig-Maximilians-University Munich, Department of Biology II, Anthropology and Human Genomics, 82152 Martinsried, Germany.
4
Ludwig-Maximilians-University Munich, Institute for Informatics, Teaching and Research Unit Bioinformatics, 80333 Munich, Germany.
5
Ludwig-Maximilians-University Munich, Faculty of Physics, Soft Condensed Matter Group, 80539 Munich, Germany.
6
Ludwig-Maximilians-University Munich, Department of Pharmacy, Center for Drug Research, 81377 Munich, Germany stefan.zahler@cup.uni-muenchen.de.

Abstract

Developmental processes, such as angiogenesis, are associated with a constant remodeling of the actin cytoskeleton in response to different mechanical stimuli. The mechanosensitive transcription factors MRTF-A (MKL1) and YAP (also known as YAP1) are important mediators of this challenging adaptation process. However, it is as yet unknown whether both pathways respond in an identical or in a divergent manner to a given microenvironmental guidance cue. Here, we use a micropatterning approach to dissect single aspects of cellular behavior in a spatiotemporally controllable setting. Using the exemplary process of angiogenesis, we show that cell-cell contacts and adhesive surface area are shared regulatory parameters of MRTF and YAP on rigid 2D surfaces. By analyzing MRTF and YAP under laminar flow conditions and during cell migration on dumbbell-shaped microstructures, we demonstrate that they exhibit different translocation kinetics. In conclusion, our work promotes the application of micropatterning techniques as a cell biological tool to study mechanosensitive signaling in the context of angiogenesis.

KEYWORDS:

Endothelial cell; MLK1; MRTF; Mechanosensing; Micropatterning; YAP

PMID:
29724912
DOI:
10.1242/jcs.212886
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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