title: Remodeling of fibrous extracellular matrices by contractile cells: predictions from discrete fiber network simulations.
abstract: Contractile forces exerted on the surrounding extracellular matrix (ECM) lead to the alignment and stretching of constituent fibers within the vicinity of cells. As a consequence, the matrix reorganizes to form thick bundles of aligned fibers that enable force transmission over distances larger than the size of the cells. Contractile force-mediated remodeling of ECM fibers has bearing on a number of physiologic and pathophysiologic phenomena. In this work, we present a computational model to capture cell-mediated remodeling within fibrous matrices using finite element-based discrete fiber network simulations. The model is shown to accurately capture collagen alignment, heterogeneous deformations, and long-range force transmission observed experimentally. The zone of mechanical influence surrounding a single contractile cell and the interaction between two cells are predicted from the strain-induced alignment of fibers. Through parametric studies, the effect of cell contractility and cell shape anisotropy on matrix remodeling and force transmission are quantified and summarized in a phase diagram. For highly contractile and elongated cells, we find a sensing distance that is ten times the cell size, in agreement with experimental observations.
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: A S
authors.initials: AS
authors.lastname: Abhilash
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Brendon M
authors.initials: BM
authors.lastname: Baker
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Britta
authors.initials: B
authors.lastname: Trappmann
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: vshenoy@seas.upenn.edu.
authors.forename: Vivek B
authors.initials: VB
authors.lastname: Shenoy
mesh_terms: D003094:Collagen / Q000737:chemistry*; D004548:Elasticity; D005109:Extracellular Matrix / Q000737:chemistry*; D056004:Molecular Dynamics Simulation
chemical_list: D003094:Collagen