ArticleAdvanced materials (Deerfield Beach, Fla.)2025
De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties.
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Article in Advanced materials (Deerfield Beach, Fla.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8citing papers in PubMed
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Who cites it
8 citing papers in PubMed.
- Shared ligand-blocking mechanism but distinct conformational modulation by α5-targeting antibodies BIIG2 and MINT1526A.Structure (London, England : 1993) · 2026Article
- The Opposite Roles of Benzo[Environment & health (Washington, D.C.) · 2026Article
- Review
- Structural basis for the differential recognition of integrin αvβ3 by rhodostomin and trimucrin.Communications biology · 2026Article
- Review
- De novo protein design: a transformative frontier in clinical protein applications.Journal of translational medicine · 2026Review
- De Novo Design of Integrin α5β1 Modulating Proteins to Enhance Biomaterial Properties.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Shared ligand-blocking mechanism but distinct conformational modulation by α5-targeting antibodies BIIG2 and MINT1526A.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
- Update of
Authors and funding
26 authors.
Xinru WangDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0001-5994-707X
Jordi Guillem-MartiBiomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain.ORCID https://orcid.org/0000-0003-0307-2221
Saurav KumarDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-0992-589X
David S LeeDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0001-6539-4272
Daniel Cabrerizo-AguadoBiomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain.ORCID https://orcid.org/0009-0006-2410-6936
Rachel WertherDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-3058-1550
Kevin Alexander Estrada AlamoDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-3829-357X
Yan Ting ZhaoDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0001-9230-7066
Adam NguyenDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-2030-2861
Irina KopyevaDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0003-3740-6971
Buwei HuangDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-0762-7178
Jing LiProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.
Yuxin HaoProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.
Xinting LiDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0001-5559-7578
Aritza Brizuela-VelascoDENS-ia Research Group, Faculty of Health Sciences, Miguel de Cervantes European University, Valladolid, Spain.ORCID https://orcid.org/0000-0001-6421-3863
Analisa MurrayDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Stacey GerbenDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0003-0313-6248
Anindya RoyDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-9766-4326
Cole A DeForestInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0003-0337-3577
Timothy SpringerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID https://orcid.org/0000-0001-6627-2904
Hannele Ruohola-BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-5588-4531
Jonathan A CooperDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID https://orcid.org/0000-0002-8626-7827
Melody G CampbellDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID https://orcid.org/0000-0003-1909-5751
Jose Maria ManeroBiomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain.ORCID https://orcid.org/0000-0002-1673-4389
Maria-Pau GinebraBiomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya - BarcelonaTech (UPC), Barcelona, Spain.ORCID https://orcid.org/0000-0002-4700-5621
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID https://orcid.org/0000-0001-7896-6217
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MInterdisciplinary Tranining in Cancer ResearchT32CA080416 · NCI · UNIVERSITY OF WASHINGTON · PI STODDARD, BARRY L. · 1998 to 2023
$9.7MComprehensive Training in Inter-Disciplinary Oral Health ResearchT90DE021984 · NIDCR · UNIVERSITY OF WASHINGTON · PI Robert Aaron Cornell · 2012 to 2026
$7.9MRegulation of cell migration and signaling by phosphotyrosine and ubiquitinR01GM109463 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A · 2014 to 2022
$3.0MGenetic underpinnings of craniofacial disorders explored with spatial sequencingR01DE033016 · NIDCR · UNIVERSITY OF WASHINGTON · PI Robert Aaron Cornell, Julie Mathieu · 2023 to 2026
$2.9MMimicking, Exploiting, and Understanding Biology's Heterogeneity in 4DR35GM138036 · NIGMS · UNIVERSITY OF WASHINGTON · PI Cole A DeForest · 2020 to 2026
$2.3MThe Molecular Basis for Integrin-Mediated Bidirectional SignalingR35GM147414 · NIGMS · FRED HUTCHINSON CANCER CENTER · PI Melody G Campbell · 2022 to 2026
$2.2MStructural Mechanism of Activation and Modulation of Tie2-mediated AngiogenesisF31HL174166 · NHLBI · FRED HUTCHINSON CANCER CENTER · PI NGUYEN, ADAM · 2024 to 2025
$89kBMGF Prometheus 63-8301-2021Boston Children's Hospital OFD/BTREC/CTRECFacultyCareerDevelopmentFellowshipDARPA program Harnessing Enzymatic Activity for Lifesaving Remedies (HEALR) HR0011-21-2-0012Defense Sciences Office, DARPA HR0011-21-2-0012Department of the Defense, Defense Threat Reduction Agency DTRAJ5B_ML-MACROCYCLES-62-5503-2021Department of the Defense, Defense Threat Reduction Agency HDTRA1-21-1-0007European Regional Development Fund PID2021-125150OB-I00Fred Hutchinson Cancer Center 2024FI-100198Fred Hutchinson Cancer Center RRIDFred Hutchinson Cancer Center SCR_022611ICREA Academia AwardNational Science Foundation DGE1762114NCI NIH HHS P30 CA015704NCI NIH HHS T32 CA080416NHLBI NIH HHS 1F31HL174166NHLBI NIH HHS F31 HL174166NHLBI NIH HHS R01-HL-131729NIDCR NIH HHS R01 DE033016NIDCR NIH HHS T90 DE021984NIGMS NIH HHS R01 GM109463NIGMS NIH HHS R35 GM138036NIGMS NIH HHS R35GM138036NIGMS NIH HHS R35 GM147414NIH HHS R01DE033016NIH HHS R01GM109463NIH HHS R01-HL-131729NIH HHS R35GM138036NIH HHS R35GM147414NIH HHS T32CA080416NIH HHS T90DE021984Pew Biomedical ScholarsSpanish National Plan for Scientific and Technical Research and Innovation RYC2022-038006-IThe Audacious Project PG117866The Audacious Project PG117878The Nordstrom Barrier Institute for Protein Design Directors Fund GF124659Universitat Politècnica de Catalunya 2021UPC-MZ-67143Wu Tsai Protein Innovation Fund GF151772
Abstract
Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins can have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin (FN) and RGD peptides in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed FN- and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.
Indexed as
Biocompatible MaterialsIntegrin alpha5beta1AnimalsCell AdhesionFibronectinsHumansHydrogelsMiceOligopeptidesTitaniumarginyl-glycyl-aspartic acidBiocompatible MaterialsFibronectinsHydrogelsIntegrin alpha5beta1OligopeptidesTitaniumbiomaterialde novo protein designhydrogelintegrin α5β1regenerative medicineRGDtitanium
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.