Cooperative effects of fibronectin matrix assembly and initial cell–substrate adhesion strength in cellular self-assembly

Abstract

The cell-dependent polymerization of intercellular fibronectin fibrils can stimulate cells to self-assemble into multicellular structures. The local physical cues that support fibronectin-mediated cellular self-assembly are largely unknown. Here, fibronectin matrix analogs were used as synthetic adhesive substrates to model cell-matrix fibronectin fibrils having different integrin-binding specificity, affinity, and/or density. We utilized this model to quantitatively assess the relationship between adhesive forces derived from cell-substrate interactions and the ability of fibronectin fibril assembly to induce cellular self-assembly. Results indicate that the strength of initial, rather than mature, cell-substrate attachments correlates with the ability of substrates to support fibronectin-mediated cellular self-assembly. The cellular response to soluble fibronectin was bimodal and independent of the integrin-binding specificity of the substrate; increasing soluble fibronectin levels above a critical threshold increased aggregate cohesion on permissive substrates. Once aggregates formed, continuous fibronectin polymerization was necessary to maintain cohesion. During self-assembly, soluble fibronectin decreased cell-substrate adhesion strength and induced aggregate cohesion via a Rho-dependent mechanism, suggesting that the balance of contractile forces derived from fibronectin fibrils within cell-cell versus cell-substrate adhesions controls self-assembly and aggregate cohesion. Thus, initial cell-substrate attachment strength may provide a quantitative basis with which to build predictive models of fibronectin-mediated microtissue fabrication on a variety of substrates.

Acoustic modification of collagen hydrogels facilitates cellular remodeling

“…For these studies, the collagen concentration was increased to 2.0 mg/mL, which eliminated the central pore introduced by US exposure and allowed for the homogenous distribution of cells on the gel surface. The number of cells adherent 20 min after seeding was used as an indicator of initial adhesion strength [33]. Compared with sham-exposed controls, cell attachment to the US-exposed region was significantly reduced on collagen gels polymerized during exposure to 8.8-MHz US at an intensity of 8 W/cm 2 (Fig.…”

Plasma-Coated Polycaprolactone Nanofibers with Covalently Bonded Platelet-Rich Plasma Enhance Adhesion and Growth of Human Fibroblasts

“…This can be explained by the fact that poor initial cell attachment to the substrate leads to the fibronectin turnover shift to the intercellular contacts instead of the cell–matrix contacts [29,45]. The increased cell-to-cell contact creates an area of an increased tension and leads to the cell detachment from the substrate [46].…”

Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells

“…, 2011; Hsia et al. , 2014; Brennan and Hocking, 2016). It is increasingly appreciated that polymerized forms of ECM proteins elicit phenotypic changes distinct from their monomeric forms (Morla et al.…”