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An actin length threshold regulates adhesion maturation at the lamellipodium/lamellum interface


Loosli, Y; Labouesse, C; Luginbuehl, R; Meister, J-J; Snedeker, J G; Vianay, B (2013). An actin length threshold regulates adhesion maturation at the lamellipodium/lamellum interface. Integrative Biology, 5(6):865-876.

Abstract

The mechanical coupling between adherent cells and their substrates is a major driver of downstream behavior. This coupling relies on the formation of adhesion sites and actin bundles. How cells generate these elements remains only partly understood. A potentially important mechanism, the length threshold maturation (LTM), has previously been proposed to regulate adhesion maturation and actin bundle stabilization tangential to the leading edge. The LTM describes the process by which cells integrate lamellar myosin forces to trigger adhesion maturation. These forces, cumulated over the length of an actin bundle, are balanced at the anchoring focal complexes. When the bundle length exceeds a certain threshold, the distributed lamellar forces become sufficient to trigger the stabilization of the bundle and its adhesions. In this continuing study, we experimentally challenge the LTM for the first time, by seeding cells on micropatterned substrates with various non-adhesive gaps designed to selectively trigger the LTM. While stable actin bundles were observed on all patterns, their lengths were almost exclusively above 3 μm or 4 μm depending on the cell type. Furthermore, the frequency with which gaps were bridged increased nearly as a step function with increasing gap width, indicating a substrate dependent behavioral switch. These combined observations point strongly to LTM with a threshold above 3 μm. We thus experimentally confirm with two cell types our previous theoretical work postulating the existence of a length dependent threshold mechanism that triggers adhesion maturation and actin bundle stabilization.

Abstract

The mechanical coupling between adherent cells and their substrates is a major driver of downstream behavior. This coupling relies on the formation of adhesion sites and actin bundles. How cells generate these elements remains only partly understood. A potentially important mechanism, the length threshold maturation (LTM), has previously been proposed to regulate adhesion maturation and actin bundle stabilization tangential to the leading edge. The LTM describes the process by which cells integrate lamellar myosin forces to trigger adhesion maturation. These forces, cumulated over the length of an actin bundle, are balanced at the anchoring focal complexes. When the bundle length exceeds a certain threshold, the distributed lamellar forces become sufficient to trigger the stabilization of the bundle and its adhesions. In this continuing study, we experimentally challenge the LTM for the first time, by seeding cells on micropatterned substrates with various non-adhesive gaps designed to selectively trigger the LTM. While stable actin bundles were observed on all patterns, their lengths were almost exclusively above 3 μm or 4 μm depending on the cell type. Furthermore, the frequency with which gaps were bridged increased nearly as a step function with increasing gap width, indicating a substrate dependent behavioral switch. These combined observations point strongly to LTM with a threshold above 3 μm. We thus experimentally confirm with two cell types our previous theoretical work postulating the existence of a length dependent threshold mechanism that triggers adhesion maturation and actin bundle stabilization.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2013
Deposited On:13 Dec 2013 16:04
Last Modified:05 Apr 2016 17:16
Publisher:RSC Publishing
ISSN:1757-9694
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/c3ib20282h
PubMed ID:23604247

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