Year: 2026
Type: article
Abstract: Hydrogels serve as powerful models for investigating cell-extracellular matrix (ECM) interactions. While chemical modifications are routinely used to tune hydrogel properties, it remains unclear whether these modifications mediate cell fate. Previous work has shown that cells deposit newly synthesized (nascent) ECM at the cell-hydrogel interface. Here, we demonstrate that this nascent ECM interface regulates how cells interpret chemical modifications. Using hydrogels with varied chemical modifications, we isolated the effects of chemical modification on nascent ECM and cell fate. Nascent ECM deposition increased as a function of hydrogel modification and with distinct matrisome compositions. While low-modification hydrogels promoted cell differentiation, high modifications increased cell proliferation. Perturbing cell- nascent ECM interactions reversed this cell fate. Our findings reveal that nascent ECM regulates cell fate by converting hydrogel cues into signals that control cell fate. This tri-directional interplay among hydrogel chemical modifications, nascent ECM, and cell fate reframes how we interpret cell-hydrogel interactions.
Source: Advanced Science
DOI: 10.1002/advs.77895
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
Awards: G223564834, Engineered alveolar organoids to understand ECM signaling, G9000008098, G9000372685, G9000374344, Implementing the nascent ECM into the dynamic reciprocity of cell-ECM interactions, Regulation of Tendon Enthesis Development and Healing via HIF1, Cellular Biotechnology Training Program (CBTP) - Years 31-35
OpenAlex ID: W7214539487