Role of material-driven fibronectin fibrillogenesis in cell differentiation

Vitronectin as a Micromanager of Cell Response in Material‐Driven Fibronectin Nanonetworks

“…The high differentiation degree of C2C12 cells on fibrillar fibronectin has been previously reported, and correlated to the ability of cells to bind to unfolded FN and exert forces;28 besides, the fundamental role of fibronectin in myogenesis has been further established 41. On the other hand, the high level of differentiation on VN is likely linked to an earlier onset of cell fusion, as shown by observing cell differentiation over time (Figure 6).…”

“…It is established that cell adhesion and differentiation are enhanced on fibrillar FN compared to its globular solution conformation;28, 38 in particular, we observed that material‐driven FN fibrils are able to sustain high myogenic differentiation levels28 and that cell adhesion is improved with increased FN density38 or in the presence of VN 20. Here, we set out to explore short‐term cell response to the protein interface looking at cell‐mediated remodeling following cell attachment; the ability of cells to reorganize their surroundings is in fact linked to the biocompatibility of the material and its ultimate fate in vitro or in vivo 15.…”

“…[[qv: 14a,c,26]] This work builds on this concept by engineering artificial fibrillar microenvironments that exploit the interaction between one of the main structural ECM components, FN, and a particular surface chemistry, PEA. We have previously shown that this acrylate is able to trigger the cell‐free organization of FN molecules into physiological‐like nanofibrils upon adsorption of the protein onto the material surface, regardless of surface topography;18, 27 the resulting biointerface promotes cell adhesion and differentiation in vitro and supports bone regeneration in vivo 19, 28. We have also observed that other proteins or protein fragments affect this material‐driven FN assembly,20, 28 and we have identified VN as a promising candidate to alter FN organization at the cell–material interface 20.…”

“…We have previously shown that this acrylate is able to trigger the cell‐free organization of FN molecules into physiological‐like nanofibrils upon adsorption of the protein onto the material surface, regardless of surface topography;18, 27 the resulting biointerface promotes cell adhesion and differentiation in vitro and supports bone regeneration in vivo 19, 28. We have also observed that other proteins or protein fragments affect this material‐driven FN assembly,20, 28 and we have identified VN as a promising candidate to alter FN organization at the cell–material interface 20. VN is in fact a low‐molecular‐weight matricellular component of the ECM and main adhesive component of serum, known to organize and micromanage the local hydrogel milieu in vivo through interactions with several other ECM molecules;1 indeed, it forms multiprotein complexes with a repertoire of biologically active species, modulating their biological functions.…”

Mechanotransduction and Growth Factor Signalling to Engineer Cellular Microenvironments

“…ethyl -PEA, butyl -PBA, hexyl -PHA) promoted fibronectin assembly into nanonetworks (Figure 3b). [45][46][47] This assembled fibronectin structure has the ability to present GFs in synergy with α 5 β 1 integrins, i.e., the molecule is open and FNIII [9][10] and III [12][13][14] regions are simultaneously available for interaction. Indeed, using atomic force microscopy we showed that BMP-2 binds fibronectin nanonetworks previously assembled on PEA and then promotes co-localization of integrins and GF receptors resulting in enhanced canonical Smad signaling (Figure 3c).…”