title: Distinct biological events generated by ECM proteolysis by two homologous collagenases.
abstract: It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Inna
authors.initials: I
authors.lastname: Solomonov
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Eldar
authors.initials: E
authors.lastname: Zehorai
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Dalit
authors.initials: D
authors.lastname: Talmi-Frank
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Sharon G
authors.identifier: 0000-0002-5337-5063
authors.initials: SG
authors.lastname: Wolf
authors.affiliation: Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Alla
authors.initials: A
authors.lastname: Shainskaya
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Alina
authors.initials: A
authors.lastname: Zhuravlev
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Elena
authors.initials: E
authors.lastname: Kartvelishvily
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, United Kingdom;
authors.forename: Robert
authors.initials: R
authors.lastname: Visse
authors.affiliation: Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Yishai
authors.initials: Y
authors.lastname: Levin
authors.affiliation: Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Kampf
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Diego Adhemar
authors.initials: DA
authors.lastname: Jaitin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, United Kingdom;
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel; Irit.sagi@weizmann.ac.il.
authors.forename: Irit
authors.initials: I
authors.lastname: Sagi
mesh_terms: D000818:Animals; D021982:Cell-Matrix Junctions / Q000378:metabolism; D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D025341:Principal Component Analysis; D059748:Proteolysis; D051381:Rats; D012212:Rheology; D017386:Sequence Homology, Amino Acid; D014783:Viscosity
chemical_list: D003094:Collagen; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1
keywords: ECM; MMP; proteolysis