Dynamics of Tissue-Induced Alignment of Fibrous Extracellular Matrix.

TitleDynamics of Tissue-Induced Alignment of Fibrous Extracellular Matrix.
Publication TypeJournal Article
Year of Publication2017
AuthorsPiotrowski-Daspit, AS, Nerger, BA, Wolf, AE, Sundaresan, S, Nelson, CM
JournalBiophys J
Date Published2017 Aug 08
KeywordsAnimals, Cell Line, Tumor, Cell Movement, Cytoskeleton, Extracellular Matrix, Matrix Metalloproteinases, Mice, Models, Biological, Neoplasm Invasiveness

<p>Aligned fibers of extracellular matrix (ECM) affect the direction, efficiency, and persistence of migrating cells. To uncover the mechanisms by which multicellular tissues align their surrounding ECM before migration, we used an engineered three-dimensional culture model to investigate the dynamics of ECM alignment around tissues of defined geometry. Analysis of ECM alignment over time revealed that tissues rapidly reorganize their surrounding matrix, with a characteristic time that depends on the type of cell and the initial tissue geometry. We found that matrix metalloproteinase activity is not required for matrix alignment before cell migration. Instead, alignment is driven by Rho-mediated cytoskeletal contractility and accelerated by propagation of tension through intercellular adhesions. Our data suggest that multicellular tissues align their surrounding matrix by pulling collectively to exert strain, which is primarily a physical process. Consistently, the pattern of matrix alignment depends on tissue geometry and the resulting distribution of mechanical strain, with asymmetric tissues generating a higher degree of matrix alignment along their longest axes. The rapid ability of multicellular tissues to physically remodel their matrix enables their constituent cells to migrate efficiently along aligned fibers and to quickly change their direction according to other microenvironmental cues, which is important for both normal and disease processes.</p>

Alternate JournalBiophys J
PubMed ID28793224
PubMed Central IDPMC5550306
Grant ListR01 CA187692 / CA / NCI NIH HHS / United States
R01 HL120142 / HL / NHLBI NIH HHS / United States
R21 HL118532 / HL / NHLBI NIH HHS / United States