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Cell jamming in a collagen-based interface assay is tuned by collagen density and proteolysis.

Authors :
Beunk, Lianne
Nan Wen
van Helvert, Sjoerd
Bekker, Bram
Ran, Lars
Kang, Ross
Paulat, Tom
Syga, Simon
Deutsch, Andreas
Friedl, Peter
Wolf, Katarina
Source :
Journal of Cell Science. Dec2023, Vol. 136 Issue 23, p1-10. 10p.
Publication Year :
2023

Abstract

Tumor cell invasion into heterogenous interstitial tissues consisting of network-, channel-or rift-like architectures involves both matrix metalloproteinase (MMP)-mediated tissue remodeling and cell shape adaptation to tissue geometry. Three-dimensional (3D) models composed of either porous or linearly aligned architectures have added to the understanding of how physical spacing principles affect migration efficacy; however, the relative contribution of each architecture to decision making in the presence of varying MMP availability is not known. Here, we developed an interface assay containing a cleft between two high-density collagen lattices, and we used this assay to probe tumor cell invasion efficacy, invasion mode and MMP dependence in concert. In silico modeling predicted facilitated cell migration into confining clefts independently of MMP activity, whereas migration into dense porous matrix was predicted to require matrix degradation. This prediction was verified experimentally, where inhibition of collagen degradation was found to strongly compromise migration into 3D collagen in a densitydependent manner, but interface-guided migration remained effective, occurring by cell jamming. The 3D interface assay reported here may serve as a suitable model to better understand the impact of in vivo-relevant interstitial tissue topologies on tumor invasion patterning and responses to molecular interventions. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219533
Volume :
136
Issue :
23
Database :
Academic Search Index
Journal :
Journal of Cell Science
Publication Type :
Academic Journal
Accession number :
174654294
Full Text :
https://doi.org/10.1242/jcs.260207