title: Fibrin-fiber architecture influences cell spreading and differentiation.
abstract: The mechanical and structural properties of the extracellular matrix (ECM) play an important role in regulating cell fate. The natural ECM has a complex fibrillar structure and shows nonlinear mechanical properties, which are both difficult to mimic synthetically. Therefore, systematically testing the influence of ECM properties on cellular behavior is very challenging. In this work we show two different approaches to tune the fibrillar structure and mechanical properties of fibrin hydrogels. Addition of extra thrombin before gelation increases the protein density within the fibrin fibers without significantly altering the mechanical properties of the resulting hydrogel. On the other hand, by forming a composite hydrogel with a synthetic biomimetic polyisocyanide network the protein density within the fibrin fibers decreases, and the mechanics of the composite material can be tuned by the PIC/fibrin mass ratio. The effect of the changes in gel structure and mechanics on cellular behavior are investigated, by studying human mesenchymal stem cell (hMSC) spreading and differentiation on these gels. We find that the trends observed in cell spreading and differentiation cannot be explained by the bulk mechanics of the gels, but correlate to the density of the fibrin fibers the gels are composed of. These findings strongly suggest that the microscopic properties of individual fibers in fibrous networks play an essential role in determining cell behavior.
authors.affiliation: a Institute for Molecules and Materials, Radboud University , Nijmegen , The Netherlands.
authors.forename: Stéphanie M C
authors.initials: SM
authors.lastname: Bruekers
authors.affiliation: a Institute for Molecules and Materials, Radboud University , Nijmegen , The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Jaspers
authors.affiliation: a Institute for Molecules and Materials, Radboud University , Nijmegen , The Netherlands.
authors.forename: José M A
authors.initials: JM
authors.lastname: Hendriks
authors.affiliation: b Systems Biophysics Department, FOM Institute AMOLF , Amsterdam , The Netherlands.|c Department of Biomedical Engineering , Eindhoven University of Technology , Eindhoven , The Netherlands.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kurniawan
authors.affiliation: b Systems Biophysics Department, FOM Institute AMOLF , Amsterdam , The Netherlands.
authors.forename: Gijsje H
authors.initials: GH
authors.lastname: Koenderink
authors.affiliation: a Institute for Molecules and Materials, Radboud University , Nijmegen , The Netherlands.
authors.forename: Paul H J
authors.initials: PH
authors.lastname: Kouwer
authors.affiliation: a Institute for Molecules and Materials, Radboud University , Nijmegen , The Netherlands.|d Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane , Australia.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Rowan
authors.affiliation: a Institute for Molecules and Materials, Radboud University , Nijmegen , The Netherlands.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: T S Huck
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D055119:Elastic Modulus / Q000187:drug effects; D005337:Fibrin / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D005337:Fibrin
keywords: differentiation; fiber architecture; fibrin; hydrogels; mechanotransduction; mesenchymal stem cells; rheology; strain stiffening; turbidity