TY - JOUR

T1 - Binding Revisited - Avidity in Cellular Function and Signaling

AU - Erlendsson, Simon

AU - Teilum, Kaare

PY - 2021

Y1 - 2021

N2 - When characterizing biomolecular interactions, avidity, is an umbrella term used to describe the accumulated strength of multiple specific and unspecific interactions between two or more interaction partners. In contrast to the affinity, which is often sufficient to describe monovalent interactions in solution and where the binding strength can be accurately determined by considering only the relationship between the microscopic association and dissociation rates, the avidity is a phenomenological macroscopic parameter linked to several microscopic events. Avidity also covers potential effects of reduced dimensionality and/or hindered diffusion observed at or near surfaces e.g., at the cell membrane. Avidity is often used to describe the discrepancy or the "extra on top" when cellular interactions display binding that are several orders of magnitude stronger than those estimated in vitro. Here we review the principles and theoretical frameworks governing avidity in biological systems and the methods for predicting and simulating avidity. While the avidity and effects thereof are well-understood for extracellular biomolecular interactions, we present here examples of, and discuss how, avidity and the underlying kinetics influences intracellular signaling processes.

AB - When characterizing biomolecular interactions, avidity, is an umbrella term used to describe the accumulated strength of multiple specific and unspecific interactions between two or more interaction partners. In contrast to the affinity, which is often sufficient to describe monovalent interactions in solution and where the binding strength can be accurately determined by considering only the relationship between the microscopic association and dissociation rates, the avidity is a phenomenological macroscopic parameter linked to several microscopic events. Avidity also covers potential effects of reduced dimensionality and/or hindered diffusion observed at or near surfaces e.g., at the cell membrane. Avidity is often used to describe the discrepancy or the "extra on top" when cellular interactions display binding that are several orders of magnitude stronger than those estimated in vitro. Here we review the principles and theoretical frameworks governing avidity in biological systems and the methods for predicting and simulating avidity. While the avidity and effects thereof are well-understood for extracellular biomolecular interactions, we present here examples of, and discuss how, avidity and the underlying kinetics influences intracellular signaling processes.

KW - avidity

KW - functional affinity

KW - retention time

KW - cellular avidity

KW - modeling avidity

KW - SURFACE-PLASMON RESONANCE

KW - QUARTZ-CRYSTAL MICROBALANCE

KW - SUPPORTED LIPID-BILAYERS

KW - COLI RNA-POLYMERASE

KW - MULTIVALENT INTERACTIONS

KW - RECEPTOR-BINDING

KW - RESIDENCE TIME

KW - LINKER LENGTH

KW - HIGH-AFFINITY

KW - LIGAND

U2 - 10.3389/fmolb.2020.615565

DO - 10.3389/fmolb.2020.615565

M3 - Review

C2 - 33521057

VL - 7

JO - Frontiers in Molecular Biosciences

JF - Frontiers in Molecular Biosciences

SN - 2296-889X

M1 - 615565

ER -