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Extracellular Peptide-Ligand Dimerization Actuator Receptor Design for Reversible and Spatially Dosed 3D
Matthias Recktenwald1, Ritankar Bhattacharya2, Mohammed Mehdi Benmassaoud1
1Department of Biomedical Engineering, Rowan University, 201 Mullica Hill Rd, Glassboro, New Jersey 08028, United States.
ACS Synthetic Biology
|December 20, 2024
Summary
Scientists developed a new synthetic receptor platform, the Extracellular Peptide-ligand Dimerization Actuator (EPDA), to control mammalian cell responses to biomaterials. This breakthrough enables precise, reversible cellular activation or inhibition on 3D material surfaces.
Area of Science:
- Biomaterials Science
- Synthetic Biology
- Cellular Engineering
Background:
- Mammalian cells require transmembrane receptors to interact with biomaterial-bound ligands, a crucial link between synthetic biology and biomaterials.
- Thiol-norbornene chemistry allows for precise thiol-peptide patterning on materials, creating a foundation for advanced biomaterial design.
Purpose of the Study:
- To rationally design synthetic receptors that reversibly activate cellular responses based on peptide-ligand recognition on biomaterials.
- To develop a platform for controlling cellular behavior in 3D biomaterial environments.
Main Methods:
- Development of the Extracellular Peptide-ligand Dimerization Actuator (EPDA) platform, featuring stimulatory and inhibitory receptor pairs.
- Computational design of over 2000 monobodies using the novel PETEI algorithm to identify optimal ligand-receptor pairs.
- Experimental validation of monobodies and integration into EPDA receptors, with cellular responses monitored via green fluorescent protein (GFP) merging.
Main Results:
- EPDA receptors successfully mediated reversible cellular responses, including intracellular protein merging (GFP fluorescence), in a dose- and time-dependent manner.
- EPDA-programmed cells within thiol-norbornene hydrogels showed location-specific 3D activation or deactivation based on patterned peptide ligands.
- Demonstrated the ability of EPDA receptors to recognize diverse peptide-ligands on 3D materials and induce tunable cellular activities.
Conclusions:
- The EPDA platform provides a versatile tool for controlling mammalian cell behavior through biomaterial-bound peptide recognition.
- EPDA technology offers broad applicability in biological research, regenerative medicine, and the development of advanced smart biomaterials.
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