title: Vinculin facilitates cell invasion into three-dimensional collagen matrices.
abstract: The cytoskeletal protein vinculin contributes to the mechanical link of the contractile actomyosin cytoskeleton to the extracellular matrix (ECM) through integrin receptors. In addition, vinculin modulates the dynamics of cell adhesions and is associated with decreased cell motility on two-dimensional ECM substrates. The effect of vinculin on cell invasion through dense three-dimensional ECM gels is unknown. Here, we report how vinculin expression affects cell invasion into three-dimensional collagen matrices. Cell motility was investigated in vinculin knockout and vinculin expressing wild-type mouse embryonic fibroblasts. Vinculin knockout cells were 2-fold more motile on two-dimensional collagen-coated substrates compared with wild-type cells, but 3-fold less invasive in 2.4 mg/ml three-dimensional collagen matrices. Vinculin knockout cells were softer and remodeled their cytoskeleton more dynamically, which is consistent with their enhanced two-dimensional motility but does not explain their reduced three-dimensional invasiveness. Importantly, vinculin-expressing cells adhered more strongly to collagen and generated 3-fold higher traction forces compared with vinculin knockout cells. Moreover, vinculin-expressing cells were able to migrate into dense (5.8 mg/ml) three-dimensional collagen matrices that were impenetrable for vinculin knockout cells. These findings suggest that vinculin facilitates three-dimensional matrix invasion through up-regulation or enhanced transmission of traction forces that are needed to overcome the steric hindrance of ECMs.
authors.affiliation: Center for Medical Physics and Technology, Biophysics Group, Friedrich-Alexander-University of Erlangen-Nuremberg, 91052 Erlangen, Germany. claudia.mierke@t-online.de
authors.forename: Claudia T
authors.initials: CT
authors.lastname: Mierke
authors.forename: Philip
authors.initials: P
authors.lastname: Kollmannsberger
authors.forename: Daniel Paranhos
authors.initials: DP
authors.lastname: Zitterbart
authors.forename: Gerold
authors.initials: G
authors.lastname: Diez
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Koch
authors.forename: Susanna
authors.initials: S
authors.lastname: Marg
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Ziegler
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Goldmann
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016596:Vinculin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016596:Vinculin; D003094:Collagen