Shrink Wrapping Cells in a Defined Extracellular Matrix to Modulate the Chemo-Mechanical Microenvironment
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Cell–matrix interactions are important for the physical integration of cells into tissues and the function of insoluble, mechanosensitive signaling networks. Studying these interactions in vitro can be difficult because the extracellular matrix (ECM) proteins that adsorb to in vitro cell culture surfaces do not fully recapitulate the ECM-dense basement membranes to which cells such as cardiomyocytes and endothelial cells adhere to in 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.
KeywordsFibronectin Laminin Collagen Type IV Fribrinogen Myocyte Encapsulation Surface-initiated assembly c2c12
Financial support was provided to R.N.P from the Fox Center for Vision Restoration OTERO program, to J.M.S. from the NIH Biomechanics in Regenerative Medicine T32 Training Program (2T32EB003392) and to A.W.F. from the NIH Director’s New Innovator Award (1DP2HL117750).
Conflict of interest
Rachelle N. Palchesko, John M. Szymanski, Amrita Sahu and Adam W. Feinberg declare that they have no conflicts of interest.
No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.
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