Fibronectin fibril alignment is established upon initiation of extracellular matrix assembly.

TitleFibronectin fibril alignment is established upon initiation of extracellular matrix assembly.
Publication TypeJournal Article
Year of Publication2021
AuthorsGarrison, CM, Schwarzbauer, JE
JournalMol Biol Cell
Volume32
Issue8
Pagination739-752
Date Published2021 04 15
ISSN1939-4586
KeywordsAnimals, Binding Sites, Cell Culture Techniques, Cytoskeleton, Extracellular Matrix, Fibroblasts, Fibronectins, Humans, Mice, NIH 3T3 Cells, Protein Binding, Signal Transduction, Transforming Growth Factor beta, Transforming Growth Factor beta1
Abstract

<p>The physical structure of the extracellular matrix (ECM) is tissue-specific and fundamental to normal tissue function. Proper alignment of ECM fibers is essential for the functioning of a variety of tissues. While matrix assembly in general has been intensively investigated, little is known about the mechanisms required for formation of aligned ECM fibrils. We investigated the initiation of fibronectin (FN) matrix assembly using fibroblasts that assemble parallel ECM fibrils and found that matrix assembly sites, where FN fibrillogenesis is initiated, were oriented in parallel at the cell poles. We show that these polarized matrix assembly sites progress into fibrillar adhesions and ultimately into aligned FN fibrils. Cells that assemble an unaligned meshwork matrix form matrix assembly sites around the cell periphery, but the distribution of matrix assembly sites in these cells could be modulated through micropatterning or mechanical stretch. While an elongated cell shape corresponds with a polarized matrix assembly site distribution, these two features are not absolutely linked, since we discovered that transforming growth factor beta (TGF-β1) enhances matrix assembly site polarity and assembly of aligned fibrils independent of cell elongation. We conclude that the ultimate orientation of FN fibrils is determined by the alignment and distribution of matrix assembly sites that form during the initial stages of cell-FN interactions.</p>

DOI10.1091/mbc.E20-08-0533
Alternate JournalMol Biol Cell
PubMed ID33625865
PubMed Central IDPMC8108514
Grant ListR01 AR073236 / AR / NIAMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States