A new mechanism of fibronectin fibril assembly revealed by live imaging and super-resolution microscopy.

TitleA new mechanism of fibronectin fibril assembly revealed by live imaging and super-resolution microscopy.
Publication TypeJournal Article
Year of Publication2022
AuthorsTomer, D, Arriagada, C, Munshi, S, Alexander, BE, French, B, Vedula, P, Caorsi, V, House, A, Guvendiren, M, Kashina, A, Schwarzbauer, JE, Astrof, S
JournalJ Cell Sci
Volume135
Issue16
Date Published2022 Aug 15
ISSN1477-9137
KeywordsEpitopes, Extracellular Matrix, Fibronectins, Microscopy, Peptides
Abstract

<p>Fibronectin (Fn1) fibrils have long been viewed as continuous fibers composed of extended, periodically aligned Fn1 molecules. However, our live-imaging and single-molecule localization microscopy data are inconsistent with this traditional view and show that Fn1 fibrils are composed of roughly spherical nanodomains containing six to eleven Fn1 dimers. As they move toward the cell center, Fn1 nanodomains become organized into linear arrays, in which nanodomains are spaced with an average periodicity of 105±17 nm. Periodical Fn1 nanodomain arrays can be visualized between cells in culture and within tissues; they are resistant to deoxycholate treatment and retain nanodomain periodicity in the absence of cells. The nanodomain periodicity in fibrils remained constant when probed with antibodies recognizing distinct Fn1 epitopes or combinations of antibodies recognizing epitopes spanning the length of Fn1. Treatment with FUD, a peptide that binds the Fn1 N-terminus and disrupts Fn1 fibrillogenesis, blocked the organization of Fn1 nanodomains into periodical arrays. These studies establish a new paradigm of Fn1 fibrillogenesis. This article has an associated First Person interview with the first author of the paper.</p>

DOI10.1242/jcs.260120
Alternate JournalJ Cell Sci
PubMed ID35851804
PubMed Central IDPMC9481930
Grant ListR01 HL103920 / HL / NHLBI NIH HHS / United States
R01 AR073236 / AR / NIAMS NIH HHS / United States
R01 HL134935 / HL / NHLBI NIH HHS / United States
R21 OD025323 / OD / NIH HHS / United States
R01 HL158049 / HL / NHLBI NIH HHS / United States
R01 HL103920 / HL / NHLBI NIH HHS / United States
/ HL / NHLBI NIH HHS / United States
R35 GM122505 / GM / NIGMS NIH HHS / United States
R01 AR073236 / AR / NIAMS NIH HHS / United States