Unlocking the Code Behind Cell Migration
Researchers at the Medical College of Wisconsin, Luxembourg Institute for Health and St. Jude Children’s Research Hospital have developed a data science framework that reveals how cells navigate the body.
By analyzing chemokines and their G protein-coupled receptors (GPCRs)—key proteins that direct cell movement—the team discovered that small disordered regions engage larger structured areas and act as unique “keys” for binding. This insight allowed scientists to tweak these regions and alter chemokine-GPCR interactions, opening new possibilities for guiding immune cells to tumors or improving therapies like bone marrow transplants. Their findings, published in Cell, shed light on processes critical to health and disease, from wound healing to cancer metastasis.
Structure Meets Disorder: Like Encryption Keys for Cells
Think of chemokines and GPCRs as a secure digital transaction. Websites use public and private keys to ensure only the right parties exchange information. Similarly, structured regions of these proteins act like public keys, while disordered regions serve as private keys. When the two match, they create a unique “chemical identifier” that tells a cell where to go.
By decoding this system, researchers can now rationally mutate these keys to redirect cell migration—potentially steering immune cells toward tumors or boosting stem cell recruitment. To accelerate innovation, the team has made their framework publicly available, paving the way for scientists and clinicians to design chemokines and receptors with unprecedented precision.
Protein Foundry supplied a large collection of native and mutant chemokines for this study.
Kleist AB, Szpakowska M, Talbot LJ, Slodkowicz G, Malinverni D, Thomas MA, Crawford KS, McGrail DJ, Dishman AF, Wedemeyer MJ, Sluter M, Yi SS, Sahni N, Peterson FC, Chevigné A, Volkman BF, Babu MM. Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network. Cell. 2025 Jun 26;188(13):3603-3622.e27. doi: 10.1016/j.cell.2025.03.046. Epub 2025 Apr 23. PMID: 40273912; PMCID: PMC12435897.
