Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions
- Resource Type
- Authors
- Esther Wershof; Anna Labernadie; Paul A. Bates; Xavier Trepat; Stefan Boeing; Danielle Park; Samantha George; Erik Sahai; Robert P. Jenkins
- Source
- Nature Materials
Nature materials
- Subject
- 02 engineering and technology
010402 general chemistry
01 natural sciences
Article
Extracellular matrix
Matrix (mathematics)
Extracellular
Humans
General Materials Science
Anisotropy
Transcription factor
Physics
Mechanical Engineering
Isotropy
Cell migration
General Chemistry
Fibroblasts
021001 nanoscience & nanotechnology
Condensed Matter Physics
Collision
0104 chemical sciences
Extracellular Matrix
Transcription Factor AP-2
Mechanics of Materials
Biophysics
0210 nano-technology
- Language
- ISSN
- 1476-1122
The isotropic or anisotropic organization of biological extracellular matrices has important consequences for tissue function. We study emergent anisotropy using fibroblasts that generate varying degrees of matrix alignment from uniform starting conditions. This reveals that the early migratory paths of fibroblasts are correlated with subsequent matrix organization. Combined experimentation and adaptation of Vicsek modelling demonstrates that the reorientation of cells relative to each other following collision plays a role in generating matrix anisotropy. We term this behaviour ‘cell collision guidance’. The transcription factor TFAP2C regulates cell collision guidance in part by controlling the expression of RND3. RND3 localizes to cell–cell collision zones where it downregulates actomyosin activity. Cell collision guidance fails without this mechanism in place, leading to isotropic matrix generation. The cross-referencing of alignment and TFAP2C gene expression signatures against existing datasets enables the identification and validation of several classes of pharmacological agents that disrupt matrix anisotropy. The generation of aligned extracellular matrices by fibroblasts is shown to depend on cell reorientation following collision, leading to closer alignment of the cells’ long axes. This cell collision guidance depends on the transcription factor TFAP2C and localized regulation of actomyosin contractility.