Thermophoretic Analysis of Biomolecules across the Nanoscales in Self-Assembled Polymeric Matrices

Research output: Contribution to journalResearch articleContributedpeer-review



Upon subjecting molecules to nonequilibrium conditions, many biophysical and biochemical features such as molecular diffusion, protein folding, dissociation constant, as well as enzyme-catalyzed reactions can be characterized in an aqueous solution. However, conducting assays under nonequilibrium conditions in complex self-assembled biomatrices (e.g., extracellular matrices) remains challenging due to the limitations associated with sample handling, reaction design, and optical detection. Herein, we present the investigation of biomolecular thermodiffusion in noncovalently assembled synthetic or naturally derived hydrogels. This approach has been demonstrated with a large variety of analytes of different sizes across the nanoscale, including small molecules, polysaccharides, proteins, DNA, and five DNA origamis of different geometries in various polymer networks. As the aggregation of analytes can be suppressed, the in-biomatrix method has also shown advantages over in-solution measurements. Remarkably, the method provides a unique opportunity to study how a thermophoretic movement of matrix surroundings can impact the thermophoretic movement of analytes, with dimensions from low to high nm and a million-fold variation in mass. Most importantly, the method is capable of measuring binding affinity in biomatrices, allowing for characterizing the protein-ligand interaction within a more biologically relevant context.


Original languageEnglish
Pages (from-to)19148-19157
Number of pages10
JournalACS applied nano materials
Issue number20
Publication statusPublished - 27 Oct 2023

External IDs

ORCID /0000-0002-6209-2364/work/150328624
ORCID /0000-0002-2213-2763/work/150329032
ORCID /0000-0002-6669-4995/work/150330451


ASJC Scopus subject areas


  • biomolecules, high throughput, nanostructures, protein-ligand interaction, self-assembled matrix, thermophoresis