Mobile cells discriminate and adapt to mechanosensory input from extracellular matrix (ECM) topographies to undergo actin-based polarization, shape change and migration. We tested ‘cell-intrinsic’ and adaptive components of actin-based cell migration in response to widely used in vitro collagen-based substrates, including a continuous 2D surface, discontinuous fibril-based surfaces (2.5D) and fibril-based 3D geometries. Migrating B16F1 mouse melanoma cells expressing GFP–actin developed striking diversity and adaptation of cytoskeletal organization and migration efficacy in response to collagen organization. 2D geometry enabled keratinocyte-like cell spreading and lamellipod-driven motility, with barrier-free movement averaging the directional vectors from one or several leading edges. 3D fibrillar collagen imposed spindle-shaped polarity with a single cylindrical actin-rich leading edge and terminal filopod-like protrusions generating a single force vector. As a mixed phenotype, 2.5D environments prompted a broad but fractalized leading lamella, with multiple terminal filopod-like protrusions engaged with collagen fibrils to generate an average directional vector from multiple, often divergent, interactions. The migratory population reached >90% of the cells with high speeds for 2D, but only 10–30% of the cells and a 3-fold lower speed range for 2.5D and 3D substrates, suggesting substrate continuity as a major determinant of efficient induction and maintenance of migration. These findings implicate substrate geometry as an important input for plasticity and adaptation of the actin cytoskeleton to cope with varying ECM topography and highlight striking preference of moving cells for 2D continuous-shaped over more complex-shaped discontinuous 2.5 and 3D substrate geometries.
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October 2014
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Conference Article|
September 18 2014
Plasticity of the actin cytoskeleton in response to extracellular matrix nanostructure and dimensionality
Josefine Starke;
Josefine Starke
1
*Department of Dermatology, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany
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Bernhard Wehrle-Haller;
Bernhard Wehrle-Haller
†Institute of Pathology, University of Geneva, Geneva, Switzerland
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Peter Friedl
Peter Friedl
2
*Department of Dermatology, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany
‡Department of Cell Biology, Radboudumc, Radboud University Nijmegen, Geert Grooteplein 26, 6500 HB Nijmegen, The Netherlands
§Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, University of Texas MD Anderson Cancer Center, Houston, TX 77030, U.S.A.
∥Cancer Genomics Centre Netherlands (CGC.nl), Utrecht, The Netherlands
2To whom correspondence should be addressed (emailP.Friedl@ncmls.ru.nl).
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Publisher: Portland Press Ltd
Received:
May 14 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (5): 1356–1366.
Article history
Received:
May 14 2014
Citation
Josefine Starke, Bernhard Wehrle-Haller, Peter Friedl; Plasticity of the actin cytoskeleton in response to extracellular matrix nanostructure and dimensionality. Biochem Soc Trans 1 October 2014; 42 (5): 1356–1366. doi: https://doi.org/10.1042/BST20140139
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