Stochastic modeling of antibody binding predicts programmable migration on antigen patterns

Abstract

Viruses and bacteria commonly exhibit spatial repetition of the surface molecules that directly interface with the host immune system. However, the complex interaction of patterned surfaces with immune molecules containing multiple binding domains is poorly understood. We developed a pipeline for constructing mechanistic models of antibody interactions with patterned antigen substrates. Our framework relies on immobilized DNA origami nanostructures decorated with precisely placed antigens. The results revealed that antigen spacing is a spatial control parameter that can be tuned to influence the antibody residence time and migration speed. The model predicts that gradients in antigen spacing can drive persistent, directed antibody migration in the direction of more stable spacing. These results depict antibody–antigen interactions as a computational system where antigen geometry constrains and potentially directs the antibody movement. We propose that this form of molecular programmability could be exploited during the co-evolution of pathogens and immune systems or in the design of molecular machines.

DNA-origami-directed virus capsid polymorphism

“…The high addressability of DNA origami, which was demonstrated with AuNPs, can be leveraged in precise attachment of a variety of cargo/targeting molecules by hybridization or intercalation. In combination with functionalization of the protein components, the resulting multipurpose system could be implemented in various fields ranging from DNA-origami-based 3D display of ligands 56 , 57 to gene delivery 58 .…”

Theoretical analysis of immunochromatographic assay and consideration of its operating parameters for efficient designing of high-sensitivity cardiac troponin I (hs-cTnI) detection

“…In case of multiplexed networks that process a low concentration analyte solution, the statistical distribution of the analyte molecules becomes important, as there could be significant statistical variation in the number of molecules per partition, and some of the partitions may not contain enough molecules to get a detectable signal for the targeted sensitivity 25 , 26 . Hence, it is necessary to avoid a Poisson distribution to make sure that even in the case of unequal distribution of the sample between the partitions, no partition is likely to be empty.…”

Synthetic Antigen-Conjugated DNA Systems for Antibody Detection and Characterization

“…More recently, the same group has also developed a mechanistic model that describes the antibody interactions with patterned antigen substrates (Figure A) . The collected SPR data have been converted into a flexible model that considers the antibody binding to the antigens as a discrete Markov process comprising two distinct states: monovalent and bivalent antibody–antigen complexes (Figure B).…”