title: Shrink Wrapping Cells in a Defined Extracellular Matrix to Modulate the Chemo-Mechanical Microenvironment.
abstract: Cell-matrix interactions are important for the physical integration of cells into tissues and the function of insoluble, mechanosensitive signaling networks. Studying these interactionsin vitrocan be difficult because the extracellular matrix (ECM) proteins that adsorb toin vitrocell culture surfaces do not fully recapitulate the ECM-dense basement membranes to which cells such as cardiomyocytes and endothelial cells adhere toin vivo. Towards addressing this limitation, we have developed a surface-initiated assembly process to engineer ECM proteins into nanostructured, microscale sheets that can be shrink wrapped around single cells and small cell ensembles to provide a functional and instructive matrix niche. Unlike current cell encapsulation technology using alginate, fibrin or other hydrogels, our engineered ECM is similar in density and thickness to native basal lamina and can be tailored in structure and composition using the proteins fibronectin, laminin, fibrinogen, and/or collagen type IV. A range of cells including C2C12 myoblasts, bovine corneal endothelial cells and cardiomyocytes survive the shrink wrapping process with high viability. Further, we demonstrate that, compared to non-encapsulated controls, the engineered ECM modulates cytoskeletal structure, stability of cell-matrix adhesions and cell behavior in 2D and 3D microenvironments.
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Rachelle N
authors.initials: RN
authors.lastname: Palchesko
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Szymanski
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Sahu
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA ; Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Feinberg
keywords: Collagen Type IV; Fibronectin; Fribrinogen; Laminin; Myocyte; c2c12; encapsulation; surface-initiated assembly