Poster 2: Cell and Tissue Studies
To The Rescue! – Altering The Fate Of Pulmonary Fibroblasts Using Cellularly And Externally Responsive Hydrogels
Breanna M. Huntington, Qi Zhang, Samantha E. Cassel, Eric M. Furst, April M. Kloxin
University of Delaware
Cells rely on detection of biophysical and biochemical cues from their microenvironment to drive a plethora of events, including proliferation and migration. In fibrotic diseases, the cellular microenvironment stiffens, and cells respond by commencing a feedback loop to uncontrollably and maladaptively remodel the extra cellular matrix (ECM). To probe and understand underlying cell-matrix interactions in this complex process, in-vitro model systems that integrate synthetic ECMs can be used for recapitulating cell-matrix interactions in three dimensions with well-defined and tunable biophysical and biochemical cues. We use a system of cellularly and externally responsive hydrogels as synthetic ECMs to mimic healthy and fibrotic cellular microenvironments. To further understand cell-matrix interactions, we use material characterizations, notably bulk rheometry and atomic force microscopy (AFM), and cellular assays, including immunostaining and a dynamic ?SMA lentiviral fibroblast reporter cell line, to assess the dynamic reciprocity and its role in cell activation in our cell culture systems. We further apply dynamic material softening events using an externally applied enzyme to alter microenvironmental mechanics and probe changes in fibroblast activation, which is a typical hallmark of fibrotic disease progression. These studies aim to provide insights into important biomechanical regulators of cellular responses and their temporal dynamics.
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