# Cooperativity transitions driven by higher-order oligomer formations in ligand-induced receptor dimerization

## TL;DR

This paper presents a model showing how higher-order oligomer formations in ligand-induced receptor dimerization can alter cooperativity from positive to negative, highlighting effects previously less studied.

## Contribution

The study introduces a multivalent receptor dimerization model that accounts for higher-order oligomers and demonstrates their impact on cooperativity shifts.

## Key findings

- Higher-order oligomers can change cooperativity sign.
- Simulations reject traditional Wofsy-Goldstein conditions.
- Oligomer formations influence receptor signaling dynamics.

## Abstract

While cooperativity in ligand-induced receptor dimerization has been linked with receptor-receptor couplings via minimal representations of physical observables, effects arising from higher-order oligomer (e.g., trimer and tetramer) formations of unobserved receptors have received less attention. Here, we propose a dimerization model of ligand-induced receptors in multivalent form representing physical observables under basis vectors of various aggregated receptor-states. Our simulations of multivalent models not only reject Wofsy-Goldstein parameter conditions for cooperativity, but show higher-order oligomer formations can shift cooperativity from positive to negative.