Focal adhesion-mediated directional cell migration guided by gradient-stretched substrate

• Published in: iScience Vol. 27; no. 8; p. 110446
• Main Authors: Chen, Zijia, Han, Xiaoning, Che, Bo, Feng, Huiping, Zhou, Yue, Deng, Linhong, Wang, Xiang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-08-2024; Elsevier
• Subjects: Haematology; Molecular biology; Transcriptomics; Molecular biology; Transcriptomics; Haematology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110446

Soft tissues experience strain under mechanical stresses, storing energy as residual stresses and strain energy. However, the specific impact of such strain on cell migration and its molecular mechanisms remains unclear. In this study, we investigated this by using polydimethylsiloxane (PDMS) membranes with varying prestrain levels but constant stiffness to mimic tissue-like conditions. Results showed that higher prestrain levels enhanced 3T3 fibroblast adhesion and reduced filopodia formation. Elevated prestrain also increased integrin and vinculin expression, which was associated with lower cell migration rates. Notably, both 3T3 fibroblasts and primary rat airway smooth muscle cells migrated faster toward higher prestrain areas on substrates with strain gradients. Knockdown of integrin or vinculin inhibited 3T3 cell migration directionality, highlighting their critical role. This research reveals a mechanobiological pathway where strain gradients direct cell migration, providing insight into a common mechanotransduction pathway influencing cellular responses to both stiffness and strain-related mechanical cues.
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•Prestrained PDMS substrates enhance cell adhesion and reduce filopodia formation•Prestrained substrates inhibit cell migration speed•Gradient-prestrained substrates induce cell migration toward high strain areas•Integrin and vinculin are crucial for gradient-strain guided directional migration
Haematology; Molecular biology; Transcriptomics