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Engineered basement membrane mimetic hydrogels to study mammary epithelial morphogenesis and invasion.


ABSTRACT: Reconstituted basement membrane products, like Matrigel, suffer from variability and xenogenic contaminants, hindering three-dimensional cell culture models. To overcome these challenges, we developed engineered basement membranes (eBMs) using peptide-conjugated alginate hydrogels with independently tunable mechanics. Ile-Lys-Val-Ala-Val (IKVAV)-modified eBMs, with fast stress relaxation and low stiffness, supported normal mammary acinus formation. Both increased stiffness and slow relaxation were required to induce invasion in IKVAV-modified eBMs, differing from the invasive phenotype observed in Arg-Gly-Asp (RGD)-modified eBMs regardless of the mechanical properties. Mechanistic studies revealed the balance of β1 and β4 integrin signaling, hemidesmosome formation, and laminin production

SUBMITTER: Baude JA 

PROVIDER: S-EPMC12466923 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature