Phenomenological and microscopic theories for catch bonds

TL;DR

This paper reviews phenomenological and microscopic theories explaining catch bonds, highlighting their successes, limitations, and the importance of physically relevant parameters, with a focus on selectin complexes and their structural basis.

Contribution

It provides a comprehensive assessment of existing theories for catch bonds, introduces a microscopic model for selectins, and emphasizes the need for more realistic simulations.

Findings

Phenomenological models fit diverse experimental data.

Microscopic theory predicts allosteric residues critical for catch bonds.

Highlighting the importance of physically meaningful parameters.

Abstract

Lifetimes of bound states of protein complexes or biomolecule folded states typically decrease when subject to mechanical force. However, a plethora of biological systems exhibit the counter-intuitive phenomenon of catch bonding, where non-covalent bonds become stronger under externally applied forces. The quest to understand the origin of catch-bond behavior has lead to the development of phenomenological and microscopic theories that can quantitatively recapitulate experimental data. Here, we assess the successes and limitations of such theories in explaining experimental data. The most widely applied approach is a phenomenological two-state model, which fits all of the available data on a variety of complexes: actomyosin, kinetochore-microtubule, selectin-ligand, and cadherin-catenin binding to filamentous actin. With a primary focus on the selectin family of cell-adhesion complexes, we discuss the positives and negatives of phenomenological models and the importance of evaluating the physical relevance of fitting parameters. We describe a microscopic theory for selectins, which provides a structural basis for catch bonds and predicts a crucial allosteric role for residues Asn82--Glu88. We emphasize the need for new theories and simulations that can mimic experimental conditions, given the complex response of cell adhesion complexes to force and their potential role in a variety of biological contexts.