Abstract
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.
Highlights
Morphogenesis is a tightly-regulated developmental process by which tissues surfaces of the body[1] or as spherical or tubular structures surrounding a central acquire the morphology that is critical to their function
We present a novel cell culture system based on PIC-Matrigel hybrid matrices composed of a natural matrix and synthetic hydrogels that is able to direct Madin-Darby Canine Kidney (MDCK) morphogenesis and can be used to explore the elements that are involved in mechanical transduction
MDCK cells develop into a broad range of morphologies, ranging from distinct round hollow cysts to extended 2D monolayers with the correct polarization, and even—in 3D—into tubular structures
Summary
Morphogenesis is a tightly-regulated developmental process by which tissues surfaces of the body[1] or as spherical or tubular structures surrounding a central acquire the morphology that is critical to their function. At higher stiffness levels and enhanced cell-matrix interactions, tuned ditions: cells typically grow into monolayer by controlling the adhesive peptide density on PIC, the hybrid hydrogels induce a flattened cell morphology with simultaneous YAP translocation, suggesting activation. Mixed synthetic and natural gels, such as the sheets when they are seeded on flat 2D substrates, and into well-organized cysts when cultured in a 3D matrix.[1] Clearly, 2D and 3D culture conditions are principally different, and at this stage it remains unclear how hybrids presented here, are ideal platforms to dissect how external physical external cues contribute to the shift from 2D factors can be used to regulate morphogenesis in MDCK model system, and monolayer sheets and 3D cysts. In vivo tissue morphogenesis is driven by forces generated by actin-myosin networks and transmitted through the cytoskeleton.[6,7] the mechanical prop-
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