# From Single Ligand–Receptor Bond Strength to Collective Avidity: Mechanics-Guided Superselective Nanoparticle Adhesion to Biological Membranes

## TL;DR

This study explores how nanoparticle mechanics and ligand-receptor interactions influence adhesion to cell membranes, offering insights for designing more selective nanomedicine.

## Contribution

The paper introduces mechanics-affinity phase diagrams to guide the design of deformable nanocarriers for superselective adhesion.

## Key findings

- Deformable nanoparticles outperform rigid ones at intermediate ligand-receptor affinities by recruiting more receptors.
- Rigid nanoparticles engage less than 10% of their ligand capacity regardless of conditions.
- Membrane tension suppresses multivalency for rigid and semirigid nanoparticles but not for deformable ones.

## Abstract

Multivalent adhesion between ligand-coated nanoparticles
(NPs)
and cell membrane receptors is central to targeted nanomedicine, yet
how NP mechanics tune the classic affinity-selectivity trade-off remains
unclear. Here we combine Monte Carlo simulations with thermodynamic
analysis to probe the binding free-energy landscape of rigid, semirigid,
and deformable NPs interacting with target receptors. By sweeping
membrane tension, receptor density, and ligand–receptor affinities
(spanning the full weak-to-strong regime), we uncover a mechanics-governed
switch in optimal design. The entropy-enthalpy compensation reveals
that deformable NPs dominate at intermediate affinities, exploiting
shape adaptability to recruit nearly all available receptors even
at low expression levels, albeit at significant entropic cost. The
semirigid NPs, in turn, require the strongest affinity to offset configurational
penalties and maximize avidity, while rigid NPs never engage more
than ∼10% of their ligand capacity. The interactions under
weak individual bonds fail to nucleate adhesion under any mechanical
or biochemical condition tested. Additionally, increasing membrane
tension selectively suppresses multivalency of binding for rigid and
semirigid NPs but leaves deformable NPs largely unaffected. The results
collapse onto mechanics-affinity phase diagrams that can predict design
windows where (super) selective adhesion emerges from the interplay
of NP stiffness, membrane deformation, bond strength, and receptor
density. These insights provide quantitative guidelines for engineering
deformable, affinity-tuned nanocarriers capable of high selectivity
under physiologically relevant mechanical and biochemical heterogeneity.