# Identification of skeletal muscle stem cell adhesion motifs using spot-synthesis-based peptide arrays

## TL;DR

This paper introduces a method using peptide arrays to identify adhesion motifs that help muscle stem cells stick better, which could lead to new treatments for muscle diseases.

## Contribution

A novel medium-throughput screening approach using SPOT-synthesized peptide arrays to identify functional ECM-derived adhesion motifs for skeletal muscle stem cells.

## Key findings

- Several ECM-derived peptide motifs were identified that enhance adhesion of muscle stem cells.
- Peptide motifs can be chemically modified for bioconjugation and in vivo basal-lamina binding.
- The method supports attachment of both healthy and dystrophic myogenic progenitor cells.

## Abstract

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.

•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

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

Biotechnology; Cell biology