title: Composite alginate gels for tunable cellular microenvironment mechanics.
abstract: The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4-12 kPa) as compared to healthy tissue (E = 0.4-2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation.
authors.affiliation: Applied Chemistry, Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.|SUMO Biomaterials VINN Excellence Center, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Adele
authors.initials: A
authors.lastname: Khavari
authors.affiliation: Applied Chemistry, Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.|UCL Australia, 220 Victoria Square, Adelaide, SA 5000 Australia.
authors.forename: Magnus
authors.initials: M
authors.lastname: Nydén
authors.affiliation: Department of Bioengineering, McGill University, Montreal Canada H3A 0C3.
authors.forename: David A
authors.initials: DA
authors.lastname: Weitz
authors.affiliation: Department of Bioengineering, McGill University, Montreal Canada H3A 0C3.|School of Engineering and Applied Sciences, Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.|Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, United States.|Harvard Medical School, Boston, Massachusetts 02115, United States.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Ehrlicher
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D008175:Lung Neoplasms / Q000556:secondary*; D008321:Mammary Glands, Animal / Q000166:cytology*; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid