Actin-driven nanotopography promotes stable integrin adhesion formation in developing tissue.

1. Nat Commun. 2024 Oct 7;15(1):8691. doi: 10.1038/s41467-024-52899-x.

Actin-driven nanotopography promotes stable integrin adhesion formation in
developing tissue.

Chen T(#)(1), Fernández-Espartero CH(#)(2)(3), Illand A(4), Tsai CT(5), Yang
Y(5), Klapholz B(2), Jouchet P(4), Fabre M(6), Rossier O(6), Cui B(5),
Lévêque-Fort S(4), Brown NH(7), Giannone G(8).

Author information:
(1)Interdisciplinary Institute for Neuroscience, Université Bordeaux, CNRS, UMR
5297, Bordeaux, France. .
(2)Department of Physiology, Development and Neuroscience, University of
Cambridge, Cambridge, UK.
(3)Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del
Rocío/CSIC/Universidad de Sevilla and Departamento de Biología Celular,
Universidad de Sevilla, Sevilla, Spain.
(4)Institut des sciences Moléculaires d’Orsay, Université Paris Saclay, CNRS,
UMR8214, Orsay, France.
(5)Department of Chemistry and Stanford Wu-Tsai Neuroscience Institute, Stanford
University, Stanford, CA, USA.
(6)Interdisciplinary Institute for Neuroscience, Université Bordeaux, CNRS, UMR
5297, Bordeaux, France.
(7)Department of Physiology, Development and Neuroscience, University of
Cambridge, Cambridge, UK. .
(8)Interdisciplinary Institute for Neuroscience, Université Bordeaux, CNRS, UMR
5297, Bordeaux, France. .
(#)Contributed equally

Morphogenesis requires building stable macromolecular structures from highly
dynamic proteins. Muscles are anchored by long-lasting integrin adhesions to
resist contractile force. However, the mechanisms governing integrin diffusion,
immobilization, and activation within developing tissues remain elusive. Here,
we show that actin polymerization-driven membrane protrusions form
nanotopographies that enable strong adhesion at Drosophila muscle attachment
sites (MASs). Super-resolution microscopy reveals that integrins assemble
adhesive belts around Arp2/3-dependent actin protrusions, forming
invadosome-like structures with membrane nanotopographies. Single protein
tracking shows that, during MAS development, integrins become immobile and
confined within diffusion traps formed by the membrane nanotopographies. Actin
filaments also display restricted motion and confinement, indicating strong
mechanical connection with integrins. Using isolated muscle cells, we show that
substrate nanotopography, rather than rigidity, drives adhesion maturation by
regulating actin protrusion, integrin diffusion and immobilization. These
results thus demonstrate that actin-polymerization-driven membrane protrusions
are essential for the formation of strong integrin adhesions sites in the
developing embryo, and highlight the important contribution of geometry to
morphogenesis.

© 2024. The Author(s).

DOI: 10.1038/s41467-024-52899-x
PMCID: PMC11458790
PMID: 39375335 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.

Auteurs Bordeaux Neurocampus