Heteromultivalency Enhances Resolution in Cellular Mechanical Sorting

Area of Science:

• Biophysics
• Molecular Engineering
• Cell Biology

Background:

• Cells interact with their environment via receptor-ligand forces, crucial for development and disease.
• Current methods for profiling cell mechanics lack precision due to limitations in ligand design.
• Discrete valency changes in conventional ligands hinder the continuous modulation of binding avidity.

Purpose of the Study:

• To introduce a bivariate strategy for constructing heteromultivalent ligands with independently tunable affinity and valency.
• To overcome the limitations of traditional homovalent ligands in achieving continuous avidity modulation.
• To enhance the sensitivity and resolution of mechanical cell profiling.

Main Methods:

• Co-assembly of two aptamers with distinct binding affinities on a DNA nanoscaffold.
• Stoichiometric modulation to precisely control ligand avidity.
• Application of heteromultivalent ligands for mechanical force measurements and cell sorting.

Main Results:

• Generation of a continuous avidity spectrum for ligands, surpassing discrete homovalent systems.
• Enhanced sensitivity in force measurements, revealing subtle mechanical differences in cells.
• Successful sequential sorting of phenotypically similar cell subpopulations using flow rate adjustments.

Conclusions:

• Avidity modulation is critical for engineering multivalent interactions and mechanical cell profiling.
• Heteromultivalent ligands offer superior advantages over homovalent strategies for precise mechanical cell analysis.
• This approach advances the ability to discern and sort cells based on nuanced mechanical phenotypes.