Saums, Michele KWang, WeifengHan, BiaoMadhavan, LakshmiLee, DaeyeonHan, LinWells, Rebecca G2023-05-222023-05-222014-05-012017-07-18https://repository.upenn.edu/handle/20.500.14332/2757Cell culture systems for studying the combined effects of matrix proteins and mechanical forces on the behavior of soft tissue cells have not been well developed. Here, we describe a new biomimetic cell culture system that allows for the study of mixtures of matrix proteins while controlling mechanical stiffness in a range that is physiological for soft tissues. This system consists of layer-by-layer (LbL)-assembled films of native matrix proteins atop mechanically tunable soft supports. We used hepatic stellate cells, which differentiate to myofibroblasts in liver fibrosis, for proof-of-concept studies. By culturing cells on collagen and lumican LbL-modified hydrogels, we demonstrate that this system is noncytotoxic and offers a valid control substrate, that the hydrogel determines the overall system mechanics, and that the addition of lumican to collagen influences the stellate cell phenotype. LbL-modified hydrogels offer the potential to study the influence of complex environmental factors on soft-tissue cells in culture.ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.lumicanhepatic stellate cellhydrogelpolyacrylamideelastic modulusliver fibrosislayer-by-layer assemblyCell and Developmental BiologyMedical NeurobiologyNeurologyNeuroscience and NeurobiologyArticle