title: The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function.
abstract: Changes in the mechanical properties of dermis occur during skin aging or tissue remodeling and affect the activity of resident fibroblasts. With the aim to establish elastic culture substrates that reproduce the variable softness of dermis, we determined Young's elastic modulus E of human dermis at the cell perception level using atomic force microscopy. The E of dermis ranged from 0.1 to 10 kPa, varied depending on body area and dermal layer, and tended to increase with age in 26-55-year-old donors. The activation state of human dermal fibroblasts cultured on "skin-soft" E (5 kPa) silicone culture substrates was compared with stiff plastic culture (GPa), collagen gel cultures (0.1-9 kPa), and fresh human dermal tissue. Fibroblasts cultured on skin-soft silicones displayed low mRNA levels of fibrosis-associated genes and increased expression of the matrix metalloproteinases (MMPs) MMP-1 and MMP-3 as compared with collagen gel and plastic cultures. The activation profile exhibited by fibroblasts on "skin-soft" silicone culture substrates was most comparable with that of human dermis than any other tested culture condition. Hence, providing biomimetic mechanical conditions generates fibroblasts that are more suitable to investigate physiologically relevant cell processes than fibroblasts spontaneously activated by stiff conventional culture surfaces.
authors.affiliation: Beiersdorf AG, Research & Development, Hamburg, Germany; These authors contributed equally to this work.
authors.forename: Volker F
authors.initials: VF
authors.lastname: Achterberg
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; These authors contributed equally to this work.
authors.forename: Lara
authors.initials: L
authors.lastname: Buscemi
authors.affiliation: Beiersdorf AG, Research & Development, Hamburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Diekmann
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Josiane
authors.initials: J
authors.lastname: Smith-Clerc
authors.affiliation: Beiersdorf AG, Research & Development, Hamburg, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Schwengler
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Meister
authors.affiliation: Beiersdorf AG, Research & Development, Hamburg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.affiliation: Beiersdorf AG, Research & Development, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gallinat
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: boris.hinz@utoronto.ca.
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001696:Biomechanical Phenomena / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000502:physiology*; D054459:Elasticity Imaging Techniques; D005109:Extracellular Matrix / Q000502:physiology* / Q000648:ultrastructure*; D005260:Female; D005347:Fibroblasts / Q000502:physiology* / Q000648:ultrastructure*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D059467:Transcriptome; D055815:Young Adult
chemical_list: C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1