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Identification of skeletal muscle stem cell adhesion motifs ...

Skip to main content Skip to article View PDF Under a Creative Commons license Open access Highlights • SPOT peptide arrays enable screening for ECM-derived adhesion motifs • ECM peptides support the attachment of healthy and dystrophic myogenic progenitors •

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Under a Creative Commons license

Open access

Highlights

  • SPOT peptide arrays enable screening for ECM-derived adhesion motifs

  • ECM peptides support the attachment of healthy and dystrophic myogenic progenitors

  • Chemical modification converts ECM peptides into adhesion receptor probes

  • ECM peptides can be configured for basal-lamina binding in vivo

Summary

Altered interactions with the extracellular matrix (ECM) represent a root cause of skeletal muscle stem cell (MuSC) dysfunction in aging and disease, underscoring the therapeutic potential of targeting adhesion receptors. Here, we describe the development of an approach for the medium-throughput screening of bioactive ECM-derived adhesion motifs using peptide arrays generated by highly parallel SPOT synthesis. Based on a library of ∼50 peptide sequences originating from ECM proteins, we identified several candidate motifs that robustly enhance the adhesion of MuSC-derived cells. We demonstrate that these peptide motifs can improve the in vitro phenotype of MuSC-derived cells isolated from dystrophic muscle and provide proof-of-concept that they can be chemically modified for efficient bioconjugation, in vivo basal-lamina-binding, and as receptor-targeting molecular probes. Altogether, our work provides a versatile toolkit for studying MuSC adhesion and uncovers a set of functional peptide motifs with translational potential for pro-regenerative therapies in skeletal muscle disorders.

Subject areas

Biotechnology

Cell biology

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These authors contributed equally

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These authors contributed equally

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© 2026 The Authors. Published by Elsevier Inc.