Probing cell signaling complexity in wound healing with engineered protein materials

The National Institute of General Medical Sciences awarded the University of New England $390,500 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to probe cell signaling complexity in wound healing using engineered protein materials.

The recipient will investigate how a protein's molecular environment influences its function and how information flows through protein-ligand interactions using engineered proteins and protein-based materials. The work employs biophysical, biochemical, cell-based, and physiological approaches to examine how ligand presentation—soluble, membrane-bound, or within biomaterials—affects receptor binding, signaling, and trafficking. The recipient has developed a stimuli-responsive elastin-like protein polymer that binds vascular endothelial growth factor receptor 1 and neuropilin-1 and influences vascular endothelial cell survival in vitro. The project will measure binding affinity, kinetics, and stoichiometry of these receptors in different presentation states and explore protein phase separation's influence on receptor interactions. Initial observations showed the polymer accelerates wound pain recovery in mice and localizes to the kidney upon systemic administration, providing opportunities to refine protein biomaterial approaches to understanding the pleiotropic functions of these receptors in pain and to investigate the kidney as a model system for studying wound healing, vascular signaling, and inflammation.

Work is performed in Portland, Maine. The performance period runs from September 1, 2026, through May 31, 2031. The award is structured as a Project Grant, a common assistance type for NIGMS investigator-initiated basic research.

Abstract

Fundamental questions in biology include how a protein's environment influences its function and how information flows from the interactions of proteins with their ligands. We use engineered proteins and protein- based materials to investigate these questions through biophysical, biochemical, cell-based, and physiological approaches. We have developed a stimuli-responsive elastin-like protein polymer that binds vegf receptor 1 (VEGFR1) and neuropilin-1 (NRP1) and influences vascular endothelial cell survival in vitro. Using this tool and related rationally-designed protein materials, we will investigate how ligand presentation-soluble, membrane- bound, or within biomaterials-affects receptor binding, signaling, and trafficking. We will measure binding affinity, kinetics, and stoichiometry of VEGFR1 and NRP1 in different presentation state and explore the influence of protein phase separation on receptor interactions. Additionally, we have observed that our polymer accelerates recovery from wound pain in mice, providing an opportunity to refine protein biomaterials-based approaches to understanding the pleiotropic functions of VEGFR1 and NRP1 in pain. Our polymer also localizes to the kidney upon systemic administration in mice. Given the kidney's complex microvasculature and the availability of glomerular filtration as a well-defined, non-invasive functional readout, we will investigate the potential of the kidney as an internal model system for studying wound healing, including vascular signaling and inflammation. The successful completion of this work will advance fundamental understanding of protein- receptor interactions in different molecular contexts, develop a suite of engineered protein tools for dynamic biomaterials, and establish new models and methodologies for probing cell-cell communication through receptor-ligand interactions. By advancing our understanding of protein-receptor interactions and biomaterial- based signaling modulation, this work will provide new molecular frameworks and methodological tools applicable across diverse biological systems.