N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity

Eva Barcelona-Estaje; Mariana A G Oliva; Finlay Cunniffe; Aleixandre Rodrigo-Navarro; Paul Genever; Matthew J Dalby; Pere Roca-Cusachs; Marco Cantini; Manuel Salmeron-Sanchez

doi:10.1038/s41467-024-53107-6

N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity

Eva Barcelona-Estaje, Mariana A G Oliva, Finlay Cunniffe, Aleixandre Rodrigo-Navarro, Paul Genever, Matthew J Dalby, Pere Roca-Cusachs, Marco Cantini, Manuel Salmeron-Sanchez

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Mesenchymal stem cells (MSCs) interact with their surroundings via integrins, which link to the actin cytoskeleton and translate physical cues into biochemical signals through mechanotransduction. N-cadherins enable cell-cell communication and are also linked to the cytoskeleton. This crosstalk between integrins and cadherins modulates MSC mechanotransduction and fate. Here we show the role of this crosstalk in the mechanosensing of viscosity using supported lipid bilayers as substrates of varying viscosity. We functionalize these lipid bilayers with adhesion peptides for integrins (RGD) and N-cadherins (HAVDI), to demonstrate that integrins and cadherins compete for the actin cytoskeleton, leading to an altered MSC mechanosensing response. This response is characterised by a weaker integrin adhesion to the environment when cadherin ligation occurs. We model this competition via a modified molecular clutch model, which drives the integrin/cadherin crosstalk in response to surface viscosity, ultimately controlling MSC lineage commitment.

Original language	English
Article number	8824
Number of pages	12
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-53107-6
Publication status	Published - 12 Oct 2024

Bibliographical note

Keywords

Cadherins/metabolism
Integrins/metabolism
Viscosity
Mesenchymal Stem Cells/metabolism
Humans
Mechanotransduction, Cellular
Lipid Bilayers/metabolism
Cell Adhesion
Actin Cytoskeleton/metabolism
Cell Communication
Animals
Oligopeptides/metabolism

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10.1038/s41467-024-53107-6Licence: CC BY

s41467-024-53107-6
© The Author(s) 2024
Final published version, 3.47 MBLicence: CC BY

Cite this

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title = "N-cadherin crosstalk with integrin weakens the molecular clutch in response to surface viscosity",

abstract = "Mesenchymal stem cells (MSCs) interact with their surroundings via integrins, which link to the actin cytoskeleton and translate physical cues into biochemical signals through mechanotransduction. N-cadherins enable cell-cell communication and are also linked to the cytoskeleton. This crosstalk between integrins and cadherins modulates MSC mechanotransduction and fate. Here we show the role of this crosstalk in the mechanosensing of viscosity using supported lipid bilayers as substrates of varying viscosity. We functionalize these lipid bilayers with adhesion peptides for integrins (RGD) and N-cadherins (HAVDI), to demonstrate that integrins and cadherins compete for the actin cytoskeleton, leading to an altered MSC mechanosensing response. This response is characterised by a weaker integrin adhesion to the environment when cadherin ligation occurs. We model this competition via a modified molecular clutch model, which drives the integrin/cadherin crosstalk in response to surface viscosity, ultimately controlling MSC lineage commitment.",

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AU - Barcelona-Estaje, Eva

AU - Oliva, Mariana A G

AU - Cunniffe, Finlay

AU - Rodrigo-Navarro, Aleixandre

AU - Genever, Paul

AU - Dalby, Matthew J

AU - Roca-Cusachs, Pere

AU - Cantini, Marco

AU - Salmeron-Sanchez, Manuel

PY - 2024/10/12

Y1 - 2024/10/12

N2 - Mesenchymal stem cells (MSCs) interact with their surroundings via integrins, which link to the actin cytoskeleton and translate physical cues into biochemical signals through mechanotransduction. N-cadherins enable cell-cell communication and are also linked to the cytoskeleton. This crosstalk between integrins and cadherins modulates MSC mechanotransduction and fate. Here we show the role of this crosstalk in the mechanosensing of viscosity using supported lipid bilayers as substrates of varying viscosity. We functionalize these lipid bilayers with adhesion peptides for integrins (RGD) and N-cadherins (HAVDI), to demonstrate that integrins and cadherins compete for the actin cytoskeleton, leading to an altered MSC mechanosensing response. This response is characterised by a weaker integrin adhesion to the environment when cadherin ligation occurs. We model this competition via a modified molecular clutch model, which drives the integrin/cadherin crosstalk in response to surface viscosity, ultimately controlling MSC lineage commitment.

AB - Mesenchymal stem cells (MSCs) interact with their surroundings via integrins, which link to the actin cytoskeleton and translate physical cues into biochemical signals through mechanotransduction. N-cadherins enable cell-cell communication and are also linked to the cytoskeleton. This crosstalk between integrins and cadherins modulates MSC mechanotransduction and fate. Here we show the role of this crosstalk in the mechanosensing of viscosity using supported lipid bilayers as substrates of varying viscosity. We functionalize these lipid bilayers with adhesion peptides for integrins (RGD) and N-cadherins (HAVDI), to demonstrate that integrins and cadherins compete for the actin cytoskeleton, leading to an altered MSC mechanosensing response. This response is characterised by a weaker integrin adhesion to the environment when cadherin ligation occurs. We model this competition via a modified molecular clutch model, which drives the integrin/cadherin crosstalk in response to surface viscosity, ultimately controlling MSC lineage commitment.

KW - Cadherins/metabolism

KW - Integrins/metabolism

KW - Viscosity

KW - Mesenchymal Stem Cells/metabolism

KW - Humans

KW - Mechanotransduction, Cellular

KW - Lipid Bilayers/metabolism

KW - Cell Adhesion

KW - Actin Cytoskeleton/metabolism

KW - Cell Communication

KW - Animals

KW - Oligopeptides/metabolism

U2 - 10.1038/s41467-024-53107-6

DO - 10.1038/s41467-024-53107-6

M3 - Article

C2 - 39394209

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

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