title: Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments.
abstract: To investigate how cells sense stiffness in settings structurally similar to native extracellular matrices, we designed a synthetic fibrous material with tunable mechanics and user-defined architecture. In contrast to flat hydrogel surfaces, these fibrous materials recapitulated cell-matrix interactions observed with collagen matrices including stellate cell morphologies, cell-mediated realignment of fibres, and bulk contraction of the material. Increasing the stiffness of flat hydrogel surfaces induced mesenchymal stem cell spreading and proliferation; however, increasing fibre stiffness instead suppressed spreading and proliferation for certain network architectures. Lower fibre stiffness permitted active cellular forces to recruit nearby fibres, dynamically increasing ligand density at the cell surface and promoting the formation of focal adhesions and related signalling. These studies demonstrate a departure from the well-described relationship between material stiffness and spreading established with hydrogel surfaces, and introduce fibre recruitment as a previously undescribed mechanism by which cells probe and respond to mechanics in fibrillar matrices.
authors.affiliation: Tissue Microfabrication Lab, Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.|Wyss Institute for Biologically Inspired Engineering, Center for Life Science Boston Building, 5th Floor, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.
authors.forename: Brendon M
authors.initials: BM
authors.lastname: Baker
authors.affiliation: Tissue Microfabrication Lab, Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.|Wyss Institute for Biologically Inspired Engineering, Center for Life Science Boston Building, 5th Floor, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Trappmann
authors.affiliation: Tissue Microfabrication Lab, Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: William Y
authors.initials: WY
authors.lastname: Wang
authors.affiliation: Institute of Robotics and Intelligent Systems, Eidgenössische Technische Hochschule Zürich, CH-8092 Zürich, Switzerland.
authors.forename: Mahmut S
authors.initials: MS
authors.lastname: Sakar
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Iris L
authors.initials: IL
authors.lastname: Kim
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Vivek B
authors.initials: VB
authors.lastname: Shenoy
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.affiliation: Tissue Microfabrication Lab, Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.|Wyss Institute for Biologically Inspired Engineering, Center for Life Science Boston Building, 5th Floor, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
mesh_terms: D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D008024:Ligands; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000166:cytology
chemical_list: D008024:Ligands