title: Synthetic matrices reveal contributions of ECM biophysical and biochemical properties to epithelial morphogenesis.
abstract: Epithelial cells cultured within collagen and laminin gels proliferate to form hollow and polarized spherical structures, recapitulating the formation of a rudimentary epithelial organ. However, the contributions of extracellular matrix (ECM) biochemical and biophysical properties to morphogenesis are poorly understood because of uncontrolled presentation of multiple adhesive ligands, limited control over mechanical properties, and lot-to-lot compositional variability in these natural ECMs. We engineered synthetic ECM-mimetic hydrogels with independent control over adhesive ligand density, mechanical properties, and proteolytic degradation to study the impact of ECM properties on epithelial morphogenesis. Normal cyst growth, polarization, and lumen formation were restricted to a narrow range of ECM elasticity, whereas abnormal morphogenesis was observed at lower and higher elastic moduli. Adhesive ligand density dramatically regulated apicobasal polarity and lumenogenesis independently of cell proliferation. Finally, a threshold level of ECM protease degradability was required for apicobasal polarity and lumen formation. This synthetic ECM technology provides new insights into how cells transduce ECM properties into complex morphogenetic behaviors.
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Nduka O
authors.initials: NO
authors.lastname: Enemchukwu
authors.affiliation: Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332 Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Cruz-Acuña
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Tom
authors.initials: T
authors.lastname: Bongiorno
authors.affiliation: Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332 Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Johnson
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: José R
authors.initials: JR
authors.lastname: García
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Todd
authors.initials: T
authors.lastname: Sulchek
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332 andres.garcia@me.gatech.edu.
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D055592:Biophysical Phenomena; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism*; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D009024:Morphogenesis
chemical_list: D020100:Hydrogels