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
Date Published2022 Jul 19
ISSN1477-9137
Abstract

<p>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 (SMLM) are inconsistent with this traditional view and show Fn1 fibrils composed of roughly spherical nanodomains containing 6-11 Fn1 dimers. As they move toward the cell center, Fn1 nanodomains become organized into linear arrays, wherein nanodomains are spaced at the 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. FUD, a peptide that binds Fn1 N-terminus and disrupts Fn1 fibrillogenesis, blocks the organization of Fn1 nanodomains into periodical arrays. These studies establish a new paradigm of Fn1 fibrillogenesis.</p>

DOI10.1242/jcs.260120
Alternate JournalJ Cell Sci
PubMed ID35851804
Grant ListR01 AR073236 / AR / NIAMS NIH HHS / United States
HL103920 / GF / NIH HHS / United States
15-48571 / / National Science Foundation /
20TPA35490074 / / American Heart Association /