RT Journal Article T1 Substrate adhesion determines migration during mesenchymal cell condensation in A1 Casanellas, Ignasi A1 Jiang, Hongkai A1 David, Carolyn M. A1 Vida, Yolanda A1 Perez-Inestrosa, Ezequiel A1 Samitier, Josep A1 Lagunas, Anna K1 Cell migration K1 Mesenchymal condensation K1 Nanopatterned substrates K1 Arginine-glycine-aspartic acid K1 RGD K1 Chondrogenesis K1 N-cadherin K1 Fibronectin K1 Dynamics K1 Expression K1 Model K1 Chondrogenesis K1 Alpha-v-beta-3 K1 Gastrulation K1 Involvement K1 Mechanisms AB Mesenchymal condensation is a prevalent morphogenetic transition that is essential in chondrogenesis. However, the current understanding of condensation mechanisms is limited. In vivo, progenitor cells directionally migrate from the surrounding loose mesenchyme towards regions of increasing matrix adherence (the condensation centers), which is accompanied by the upregulation of fibronectin. Here, we focused on the mechanisms of cell migration during mesenchymal cell condensation and the effects of matrix adherence. Dendrimer-based nanopatterns of the cell-adhesive peptide arginine-glycine-aspartic acid (RGD), which is present in fibronectin, were used to regulate substrate adhesion. We recorded collective and single-cell migration of mesenchymal stem cells, under chondrogenic induction, using live-cell imaging. Our results show that the cell migration mode of single cells depends on substrate adhesiveness, and that cell directionality controls cell condensation and the fusion of condensates. Inhibition experiments revealed that cell???cell interactions mediated by N-cadherin (also known as CDH2) are also pivotal for directional migration of cell condensates by maintaining cell???cell cohesion, thus suggesting a fine interplay between cell???matrix and cell???cell adhesions. Our results shed light on the role of cell interactions with a fibronectin-depositing matrix during chondrogenesis in vitro, with possible applications in regenerative medicine. PB Company biologists ltd SN 0021-9533 YR 2022 FD 2022-11-01 LK http://hdl.handle.net/10668/20410 UL http://hdl.handle.net/10668/20410 LA en DS RISalud RD Apr 12, 2025