Initial contact guidance during cell spreading is contractility-independent

  • A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to perturb cytoskeletal structures. Inhibition of actomyosin contractility with the chemical inhibitor blebbistatatin demonstrated that initial contact guidance events are independent of traction force generation. However, cell alignment to the grooved substrate was altered at later time points, suggesting an initial ‘passive’ phase of contact guidance, followed by a contractility-dependent ‘active’ phase that relies on mechanosensitive feedback. The actin cytoskeleton was also perturbed in an indirect manner by culturing cells upside down, resulting in decreased levels of contact guidance and suggesting that a possible loss of contact between the actin cytoskeleton and the substrate could lead to cytoskeleton impairment. The process of contact guidance at the microscale was found to be primarily lamellipodia driven, as no bias in filopodia extension was observed on micron-scale grooves.

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Metadaten
Name:Kemkemer, Ralf
URN:urn:nbn:de:bsz:rt2-opus4-17448
DOI:https://doi.org/10.1039/c6sm02685k
ISSN:1744-683X
eISSN:1744-6848
Erschienen in:Soft matter
Publisher:Royal Society of Chemistry
Place of publication:London
Document Type:Article
Language:English
Year of Publication:2017
Volume:13
Issue:30
Pagenumber:10
First Page:5158
Last Page:5167
Dewey Decimal Classification:540 Chemie
Open Access:Ja
Licence (German):License Logo  Creative Commons - CC BY - Namensnennung 4.0 International