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While cooperativity in ligand-induced receptor dimerization has been linkedwith receptor-receptor couplings via minimal representations of physicalobservables, effects arising from higher-order oligomer (e.g., trimer andtetramer) formations of unobserved receptors have received less attention.Here, we propose a dimerization model of ligand-induced receptors inmultivalent form representing physical observables under basis vectors ofvarious aggregated receptor-states. Our simulations of multivalent models notonly reject Wofsy-Goldstein parameter conditions for cooperativity, but showhigher-order oligomer formations can shift cooperativity from positive tonegative.

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