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  4. Multivalent Pattern Recognition Through Engineering of Spatial Tolerance in DNA-Based Nanomaterials
 
doctoral thesis

Multivalent Pattern Recognition Through Engineering of Spatial Tolerance in DNA-Based Nanomaterials

Bila, Hale  
2022

Strength in numbers, combining many weak interactions into an overall strong connection, is the fundamental principle of multivaleny. This concept has been exploiting for the engineering of super-selective cell-targeting materials, which generally display high number of flexible ligands to enhance the systems' avidity. Many biological processes, however, function through a temporal spatial organization of receptors in patterns, matching with a controlled number of ligands to create a specific interaction. In this low-valency regime, the mechanics e.g. rigidity of the ligand-presenting architecture plays a critical role in the selectivity of the multivalent complex. Exploiting the precision in spatial design inherent to DNA nanotechnology, we engineered a library of scaffolds to explore how valency, affinity, and rigidity control the balance of super-selective multivalent binding. Depending on the affinity between the ligand and receptor, a pattern-dependent binding behavior was achieved when spatial tolerance of ligands matches the spatial organization of the target. We label this new form of mechanics-controlled multivalent binding "multivalent pattern recognition" (MPR). The main parameter controlling MPR is the rigidity of the ligand, which controls the over spatial tolerance of binding. Our findings contribute to the rational design of selective targeting with nanomaterials.

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Type
doctoral thesis
DOI
10.5075/epfl-thesis-7987
Author(s)
Bila, Hale  
Advisors
Bastings, Maartje Martina Cornelia  
Jury

Prof. Holger Frauenrath (président) ; Prof. Maartje Martina Cornelia Bastings (directeur de thèse) ; Prof. Francesco Stellacci, Prof. Björn Högberg, Prof. Patricia Dankers (rapporteurs)

Date Issued

2022

Publisher

EPFL

Publisher place

Lausanne

Public defense year

2022-05-30

Thesis number

7987

Total of pages

108

Subjects

Multivalency

•

pattern recognition

•

super-selectivity

•

DNA-based nanomaterials

•

spatial tolerance

EPFL units
PBL  
Faculty
STI  
School
IMX  
Doctoral School
EDMX  
Available on Infoscience
May 13, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/187847
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