{"id":{"repo_id":"sherbrooke","oai_identifier":"oai:usherbrooke.scholaris.ca:11143/23990"},"canonical_url":"https://search.dev.ndltd.org/etd/sherbrooke/oai:usherbrooke.scholaris.ca:11143/23990","repository":{"repo_id":"sherbrooke","name":"Université de Sherbrooke","base_url":"https://usherbrooke.scholaris.ca/server/oai/request"},"display":{"title":"Profiling muscle stem cell adhesion using extracellular matrix peptide arrays","abstract":"Aging is associated with a higher incidence of disease, which severely affects the quality of life and increases pressure on healthcare systems. Declining skeletal muscle (SkM) mass and function coupled with a reduced tissue healing capacity is one of the main drivers of loss of independence in the elderly. Our previous work revealed that aged SkM contains lower levels of certain extracellular matrix (ECM) components that are critical for proper adhesion of muscle stem cells (MuSCs), which are responsible for muscle regeneration. These observations support the notion that peptides derived from ECM proteins containing the consensus sequence for activation of adhesion receptors could have therapeutic value for the treatment of age associated MuSC dysfunction. Here we performed a medium-throughput screen using CelluSpots peptide arrays generated with the Intavis Peptide Synthesizer and a slide spotting robot to access ECM molecule derived motif’s capacity to promote adhesion of MuSC-derived primary myoblasts. Using this experimental paradigm, we identified 5 peptide sequences derived from 4 different ECM components that significantly increase adhesion of primary myoblasts. Using biotin modifications of these candidate peptides in conjunction with fluorescent streptavidin, we were able to demonstrate that they can be used as adhesion receptor probes that strongly bind the plasma membrane of primary myoblasts. In addition, we developed 2D cell culture systems to further assess effects on cell adhesion and successfully integrated an adhesion peptide to the basal lamina after in vivo delivery. Altogether, this project will lay the foundation for the development of much needed therapeutic interventions for degenerative age-associated skeletal muscle conditions.","abstract_html":"Aging is associated with a higher incidence of disease, which severely affects the quality of life and increases pressure on healthcare systems. Declining skeletal muscle (SkM) mass and function coupled with a reduced tissue healing capacity is one of the main drivers of loss of independence in the elderly. Our previous work revealed that aged SkM contains lower levels of certain extracellular matrix (ECM) components that are critical for proper adhesion of muscle stem cells (MuSCs), which are responsible for muscle regeneration. These observations support the notion that peptides derived from ECM proteins containing the consensus sequence for activation of adhesion receptors could have therapeutic value for the treatment of age associated MuSC dysfunction. Here we performed a medium-throughput screen using CelluSpots peptide arrays generated with the Intavis Peptide Synthesizer and a slide spotting robot to access ECM molecule derived motif’s capacity to promote adhesion of MuSC-derived primary myoblasts. Using this experimental paradigm, we identified 5 peptide sequences derived from 4 different ECM components that significantly increase adhesion of primary myoblasts. Using biotin modifications of these candidate peptides in conjunction with fluorescent streptavidin, we were able to demonstrate that they can be used as adhesion receptor probes that strongly bind the plasma membrane of primary myoblasts. In addition, we developed 2D cell culture systems to further assess effects on cell adhesion and successfully integrated an adhesion peptide to the basal lamina after in vivo delivery. Altogether, this project will lay the foundation for the development of much needed therapeutic interventions for degenerative age-associated skeletal muscle conditions.","abstract_has_math":false,"creators":["Leblanc, Élizabeth"],"institution":"Université de Sherbrooke","degree_name":"M. Sc.","degree_level":"Maîtrise","degree_discipline":"Pharmacologie","degree_department":null,"school":null,"contributors":[],"advisors":["Bentzinger, Conrad Florian"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023","date_published":"2023","updated_at":"2026-07-27T21:07:43Z","subjects":["Cellules souches musculaires","Matrice extracellulaire","Niche de cellules souches","Adhésion","Séquences peptidiques","Synthèse peptidique","Muscle stem cells","Myoblasts","Extracellular matrix","Adhesion motifs","Stem cell niche","Peptide sequences","Peptide synthesis"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.71892/11143/1408"],"render_values":[{"text":"https://doi.org/10.71892/11143/1408","href":"https://doi.org/10.71892/11143/1408","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/11143/23990","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bentzinger, Conrad Florian"]},{"key":"dc:creator","label":"Author","values":["Leblanc, Élizabeth"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-02-03T20:59:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2023"]},{"key":"dc:publisher","label":"Institution","values":["Université de Sherbrooke"]},{"key":"dc:type","label":"Dc Type","values":["Mémoire de maîtrise"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmacologie"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Maîtrise"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M. 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Declining skeletal muscle (SkM) mass and function coupled with a reduced tissue healing capacity is one of the main drivers of loss of independence in the elderly. Our previous work revealed that aged SkM contains lower levels of certain extracellular matrix (ECM) components that are critical for proper adhesion of muscle stem cells (MuSCs), which are responsible for muscle regeneration. These observations support the notion that peptides derived from ECM proteins containing the consensus sequence for activation of adhesion receptors could have therapeutic value for the treatment of age associated MuSC dysfunction. Here we performed a medium-throughput screen using CelluSpots peptide arrays generated with the Intavis Peptide Synthesizer and a slide spotting robot to access ECM molecule derived motif’s capacity to promote adhesion of MuSC-derived primary myoblasts. Using this experimental paradigm, we identified 5 peptide sequences derived from 4 different ECM components that significantly increase adhesion of primary myoblasts. Using biotin modifications of these candidate peptides in conjunction with fluorescent streptavidin, we were able to demonstrate that they can be used as adhesion receptor probes that strongly bind the plasma membrane of primary myoblasts. In addition, we developed 2D cell culture systems to further assess effects on cell adhesion and successfully integrated an adhesion peptide to the basal lamina after in vivo delivery. Altogether, this project will lay the foundation for the development of much needed therapeutic interventions for degenerative age-associated skeletal muscle conditions.","Le vieillissement est associé à une haute incidence de maladies qui diminuent la qualité de vie des ainées, et applique une pression sur le système de santé. Une diminution de la masse des muscles squelettiques (MSq) causée par une réduction de la capacité régénérative des cellules souches musculaires (CSMu) contribue à la perte de mobilité chez les ainées. Notre groupe de recherche a découvert que les MSq âgés contiennent une faible quantité de certaines composantes de la matrice extracellulaire (MEC), telle que la fibronectine. Nous avons observé que l'injection de certaines protéines de la MEC et l'activation forcée des récepteurs intégrines stimulent les CSMu âgées, et peuvent améliorer la régénération musculaire dans un modèle murin. L'utilisation de séquences peptidiques dérivées de protéines de la MEC pour stimuler l'adhésion des CSMu présente un réel potentiel pour le traitement des dysfonctions musculaires associées au vieillissement. Pour identifier des séquences peptidiques dérivées de protéines de la MEC (ex : laminine, collagène, fibronectine) promouvant l’adhésion des CSM, un criblage (medium-throughput screening) d'une chimiothèque de peptides d'adhésion fut effectué. Un appareil de synthèse peptidique (Intavis Peptide Synthesizer, HB Technologies Inc.) jumelé à une imprimante robotisée fût utilisé pour synthétiser 68 séquences peptidiques différentes sur un support de cellulose. En utilisant cette méthode, 5 séquences peptidiques furent identifiées comme candidats permettant d’augmenter l’adhésion des CSMu comparativement aux contrôles. Ces séquences ont ensuite été resynthétisés par synthèse sur phase solide pour tester leur potentiel à promouvoir l’adhésion des CSMu. De plus, une méthode impliquant la modification des candidats à l’aide d’une biotin couplé à une sonde fluorescente comportant une streptavidin a été développer pour visualiser la présence des séquences à la membrane plasmique des CSMu et incorporer les séquences candidates à la lame basale de souris par injection intramusculaire. En résumé, ce projet procure de l’information sur la biologie des CSMu et leurs interactions avec la MEC, mais aussi une avenue sur la mise au point d'interventions"]},{"key":"dc:title","label":"Title","values":["Profiling muscle stem cell adhesion using extracellular matrix peptide arrays"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bentzinger, Conrad Florian"],"dc:creator":["Leblanc, Élizabeth"],"dc:date.accessioned":["2026-02-03T20:59:05Z"],"dc:date.issued":["2023"],"dc:description.abstract":["Aging is associated with a higher incidence of disease, which severely affects the quality of life and increases pressure on healthcare systems. Declining skeletal muscle (SkM) mass and function coupled with a reduced tissue healing capacity is one of the main drivers of loss of independence in the elderly. Our previous work revealed that aged SkM contains lower levels of certain extracellular matrix (ECM) components that are critical for proper adhesion of muscle stem cells (MuSCs), which are responsible for muscle regeneration. These observations support the notion that peptides derived from ECM proteins containing the consensus sequence for activation of adhesion receptors could have therapeutic value for the treatment of age associated MuSC dysfunction. Here we performed a medium-throughput screen using CelluSpots peptide arrays generated with the Intavis Peptide Synthesizer and a slide spotting robot to access ECM molecule derived motif’s capacity to promote adhesion of MuSC-derived primary myoblasts. Using this experimental paradigm, we identified 5 peptide sequences derived from 4 different ECM components that significantly increase adhesion of primary myoblasts. Using biotin modifications of these candidate peptides in conjunction with fluorescent streptavidin, we were able to demonstrate that they can be used as adhesion receptor probes that strongly bind the plasma membrane of primary myoblasts. In addition, we developed 2D cell culture systems to further assess effects on cell adhesion and successfully integrated an adhesion peptide to the basal lamina after in vivo delivery. Altogether, this project will lay the foundation for the development of much needed therapeutic interventions for degenerative age-associated skeletal muscle conditions.","Le vieillissement est associé à une haute incidence de maladies qui diminuent la qualité de vie des ainées, et applique une pression sur le système de santé. Une diminution de la masse des muscles squelettiques (MSq) causée par une réduction de la capacité régénérative des cellules souches musculaires (CSMu) contribue à la perte de mobilité chez les ainées. Notre groupe de recherche a découvert que les MSq âgés contiennent une faible quantité de certaines composantes de la matrice extracellulaire (MEC), telle que la fibronectine. Nous avons observé que l'injection de certaines protéines de la MEC et l'activation forcée des récepteurs intégrines stimulent les CSMu âgées, et peuvent améliorer la régénération musculaire dans un modèle murin. L'utilisation de séquences peptidiques dérivées de protéines de la MEC pour stimuler l'adhésion des CSMu présente un réel potentiel pour le traitement des dysfonctions musculaires associées au vieillissement. Pour identifier des séquences peptidiques dérivées de protéines de la MEC (ex : laminine, collagène, fibronectine) promouvant l’adhésion des CSM, un criblage (medium-throughput screening) d'une chimiothèque de peptides d'adhésion fut effectué. Un appareil de synthèse peptidique (Intavis Peptide Synthesizer, HB Technologies Inc.) jumelé à une imprimante robotisée fût utilisé pour synthétiser 68 séquences peptidiques différentes sur un support de cellulose. En utilisant cette méthode, 5 séquences peptidiques furent identifiées comme candidats permettant d’augmenter l’adhésion des CSMu comparativement aux contrôles. Ces séquences ont ensuite été resynthétisés par synthèse sur phase solide pour tester leur potentiel à promouvoir l’adhésion des CSMu. De plus, une méthode impliquant la modification des candidats à l’aide d’une biotin couplé à une sonde fluorescente comportant une streptavidin a été développer pour visualiser la présence des séquences à la membrane plasmique des CSMu et incorporer les séquences candidates à la lame basale de souris par injection intramusculaire. En résumé, ce projet procure de l’information sur la biologie des CSMu et leurs interactions avec la MEC, mais aussi une avenue sur la mise au point d'interventions"],"dc:identifier.doi":["https://doi.org/10.71892/11143/1408"],"dc:identifier.uri":["https://hdl.handle.net/11143/23990"],"dc:language.iso":["en"],"dc:publisher":["Université de Sherbrooke"],"dc:subject":["Cellules souches musculaires","Matrice extracellulaire","Niche de cellules souches","Adhésion","Séquences peptidiques","Synthèse peptidique","Muscle stem cells","Myoblasts","Extracellular matrix","Adhesion motifs","Stem cell niche","Peptide sequences","Peptide synthesis"],"dc:title":["Profiling muscle stem cell adhesion using extracellular matrix peptide arrays"],"dc:type":["Mémoire de maîtrise"],"thesis:degree_discipline":["Pharmacologie"],"thesis:degree_level":["Maîtrise"],"thesis:degree_name":["M. Sc."],"thesis:institution_name":["Université de Sherbrooke"]},"updated_at":"2026-07-27T21:07:43Z"}