DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation
Abstract
It has been proposed that the spatial arrangement of ligands plays a key role in regulating downstream intracellular signals. Because of methodological limitations in precise ligand patterning, however, the relationship between spatial configuration of clusters and signaling dynamics remains poorly understood. By developing a DNA-based molecular “pegboard” for ligand patterning, we demonstrated that the nanometer arrangement of ligands plays significant roles in modulating signal transduction in T cells. Ligand clustering not only affects the triggering sensitivity but also determines the temporal dynamics of the intracellular signaling response. Our approach is highly translatable for studying various signaling pathways, and our results provide insights into biomolecular engineering for therapeutic uses.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 29, 2021
- Source ID
- 10.1073/pnas.2109057118
Entities
People
- Ronald D. Vale
- Ronald N. Germain
- Rui Dong
- Shawn M Douglas
- Tural Aksel
- Waipan Chan
Organizations
- Army Research Office
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Howard Hughes Medical Institute
- Jane Coffin Childs Memorial Fund for Medical Research
- National Institute of Allergy and Infectious Diseases
- National Science Foundation
- Office of Naval Research
- University of California