Tunable Hybrid Matrices Drive Epithelial Morphogenesis and YAP Translocation

Ying Zhang, Mirjam Zegers, Anika Nagelkerke, Alan Rowan, Paul Span*, Paul Kouwer*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

20 Citaten (Scopus)
35 Downloads (Pure)

Samenvatting

Morphogenesis is a tightly-regulated developmental process by which tissues acquire the morphology that is critical to their function. For example, epithelial cells exhibit different 2D and 3D morphologies, induced by distinct biochemical and biophysical cues from their environment. In this work, novel hybrid matrices composed of a Matrigel and synthetic oligo(ethylene glycol)-grafted polyisocyanides (PICs) hydrogels are used to form a highly tailorable environment. Through precise control of the stiffness and cell-matrix interactions, while keeping other properties constant, a broad range of morphologies induced in Madin-Darby Canine Kidney (MDCK) cells is observed. At relatively low matrix stiffness, a large morphological shift from round hollow cysts to 2D monolayers is observed, without concomitant translocation of the mechanotransduction protein Yes-associated protein (YAP). At higher stiffness levels and enhanced cell-matrix interactions, tuned by controlling the adhesive peptide density on PIC, the hybrid hydrogels induce a flattened cell morphology with simultaneous YAP translocation, suggesting activation. In 3D cultures, the latter matrices lead to the formation of tubular structures. Thus, mixed synthetic and natural gels, such as the hybrids presented here, are ideal platforms to dissect how external physical factors can be used to regulate morphogenesis in MDCK model system, and in the future, in more complex environments.
Originele taal-2English
Artikelnummer2003380
Aantal pagina's16
TijdschriftAdvanced science
Volume8
Nummer van het tijdschrift2
DOI's
StatusPublished - 2020
Extern gepubliceerdJa

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