Genetically programmable molecular framework for constructing precision recombinant human ECM mimics
- 1Tampere University
Abstract
Engineering extracellular matrix (ECM) mimetic materials that combine molecular precision of synthetic material options with native biological complexity remains a central challenge in biomaterials science. Here, we present a genetically programmable hydrogel platform that enables independent control of mechanical and biological properties including matrix composition, mechanics, viscoelasticity, and biochemical signaling using recombinant human ECM building blocks assembled via isopeptide chemistry. Modular protein ECM crosslinkers containing complete folded ECM domains equipped with terminal SpyTag peptides were integrated within SpyCatcher-functionalized interchangeable natural polysaccharide backbones to generate fully defined matrices with decoupled material parameters. Point mutations on crosslinker SpyTags within the bond interface varied bond affinity from covalent to physical bonding, allowing tuned stress-relaxation behaviors across physiologically relevant regimes without altering matrix composition nor stiffness. Using colorectal cancer models, we show that polymer identity and matrix viscoelasticity independently regulate spheroid growth, invasion capabilities, and dispersion. Importantly, recombinant ECM domains recapitulated native adhesion functions and provide a structurally encoded layer of biological information. This hydrogel platform provides a molecular framework for constructing precision recombinant human ECM mimics with broad applicability across biomaterials science, mechanobiology, disease modeling, tissue engineering, and regenerative medicine.
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BibTeX
@misc{evans2026genetically,
title = {{Genetically programmable molecular framework for constructing precision recombinant human ECM mimics}},
author = {A. D. Evans and J. Keranen and S. Rauhalinna and M. Mombeinipour and H. Hossain and P. Turkki and O. P. Oommen and V. P. Hytonen},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.760354},
url = {https://www.biorxiv.org/content/10.64898/2026.10.20.760354v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Genetically programmable molecular framework for constructing precision recombinant human ECM mimics
AU - A. D. Evans
AU - J. Keranen
AU - S. Rauhalinna
AU - M. Mombeinipour
AU - H. Hossain
AU - P. Turkki
AU - O. P. Oommen
AU - V. P. Hytonen
PY - 2026
DA - 2026/10/20
PB - bioRxiv
DO - 10.64898/2026.10.20.760354
UR - https://www.biorxiv.org/content/10.64898/2026.10.20.760354v1
AB - Engineering extracellular matrix (ECM) mimetic materials that combine molecular precision of synthetic material options with native biological complexity remains a central challenge in biomaterials science. Here, we present a genetically programmable hydrogel platform that enables independent control of mechanical and biological properties including matrix composition, mechanics, viscoelasticity, and biochemical signaling using recombinant human ECM building blocks assembled via isopeptide chemistry. Modular protein ECM crosslinkers containing complete folded ECM domains equipped with terminal SpyTag peptides were integrated within SpyCatcher-functionalized interchangeable natural polysaccharide backbones to generate fully defined matrices with decoupled material parameters. Point mutations on crosslinker SpyTags within the bond interface varied bond affinity from covalent to physical bonding, allowing tuned stress-relaxation behaviors across physiologically relevant regimes without altering matrix composition nor stiffness. Using colorectal cancer models, we show that polymer identity and matrix viscoelasticity independently regulate spheroid growth, invasion capabilities, and dispersion. Importantly, recombinant ECM domains recapitulated native adhesion functions and provide a structurally encoded layer of biological information. This hydrogel platform provides a molecular framework for constructing precision recombinant human ECM mimics with broad applicability across biomaterials science, mechanobiology, disease modeling, tissue engineering, and regenerative medicine.
ER -