Mammalian cells measure the extracellular matrix area and respond through switching the adhesion state

Xiaole Wang, Pengli Wang, Lihang Zhang, Tianyu Xu, Seungkuk Ahn, Upnishad Sharma, Han Yu, Nico Strohmeyer () and Daniel J. Müller ()
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Xiaole Wang: Klingelbergstrasse 48
Pengli Wang: Klingelbergstrasse 48
Lihang Zhang: Klingelbergstrasse 48
Tianyu Xu: Klingelbergstrasse 48
Seungkuk Ahn: Klingelbergstrasse 48
Upnishad Sharma: Klingelbergstrasse 48
Han Yu: Klingelbergstrasse 48
Nico Strohmeyer: Klingelbergstrasse 48
Daniel J. Müller: Klingelbergstrasse 48

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Mammalian cells adjust integrin-mediated adhesion based on the composition and structure of the extracellular matrix (ECM). However, how spatially confined ECM ligands regulate cell adhesion initiation remains unclear. Here, we investigate how cells adapt early adhesion to different ECM protein areas. Through combining microcontact printing with single-cell force spectroscopy we measure cell adhesion initiation and strengthening to defined areas of ECM proteins. HeLa cells and mouse embryonic fibroblasts gradually increase adhesion with collagen I or fibronectin area, while reaching maximum adhesion force to ECM patterns having areas above certain thresholds. On much smaller patterns, both cell types switch to a different state and considerably increase the adhesion force per ECM protein area, which they strengthen much faster. This spatially enhanced adhesion state does not require talin or kindlin, indicating a fundamentally different adhesion mechanism. Mechanotransduction seems to play integrin and cell type-specific roles in the spatially enhanced adhesion state.

Date: 2025
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DOI: 10.1038/s41467-025-62153-7

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