A catch bond mechanism with looped adhesive tethers for self-strengthening materials

Catch bonds, protein-ligand complexes exhibiting a force-enhanced lifetime, contrast sharply with slip bonds, whose lifetime decays exponentially with force. This unique property of catch bonds is crucial in various biological processes. While phenomenological and structural models for protein catch bonds exist, they lack detailed mechanistic insight. The self-strengthening and reversible nature of catch bonds are highly desirable in materials science, especially for applications requiring high resistance to failure under extreme loading conditions. Previous work by the authors demonstrated the possibility of designing shape-changing nanoparticles forming catch bonds through force-induced affinity changes; however, this approach presents significant synthetic challenges. Alternatively, nanoparticle networks held together by polymer tethers exhibiting catch bonds have been hypothesized to enhance mechanical properties. This study proposes a minimalist design using linear polymer tethers grafted onto nanoparticles and interacting with another particle via weak adhesive interactions (slip bonds) – an adhesin interaction. One tether forms a loop stabilized by a slip bond, while the other is straight. These elements, weak adhesin and loop interactions, are common in nature. The loop serves as a 'soft switch', storing length and facilitating load-sharing. This minimalistic approach avoids the complexities of designing sophisticated nanoparticle instabilities.

The authors review existing literature on catch bonds, highlighting their contrasting behavior compared to slip bonds and their importance in biological systems. They discuss existing phenomenological and structural models for catch bonds in proteins, emphasizing their limitations in providing detailed mechanistic understanding. The literature on self-strengthening materials and the potential of catch bonds in improving their mechanical properties is also reviewed. Previous modeling work by the authors on shape-changing nanoparticles and polymer-grafted nanoparticle networks is mentioned as relevant background. The ubiquity of loops in biological macromolecules and their role in imparting elasticity and sacrificial bonding (e.g., titin) is highlighted as inspiration for the proposed design.

The study employs a three-pronged approach: an analytical model, Markov Chain Monte Carlo (MCMC) simulations, and molecular dynamics (MD) simulations. The analytical model considers two identical adhesin interactions with different characteristics from the loop interaction. It defines two primary kinetic pathways for interface failure: sequential and coordinated failure. The model uses Bell's theorem to describe the kinetics of loop and adhesin interactions, deriving an analytical expression for the interface lifetime. The MCMC simulations validate the analytical predictions by modeling bond rupture and formation events using rate constants, accounting for thermal effects and force contributions. MD simulations utilize a coarse-grained representation of the system with Morse potentials representing the adhesin and loop interactions. Parameters such as the depth of the energy well (D₀), equilibrium bond distance (x₀), and the parameter controlling the width of the well (α) are varied to explore the effects on lifetime curve characteristics. Bootstrapping is used to calculate variability in lifetime data, given their non-normal distribution. The MCMC and MD simulations provide a means to test the validity and robustness of the analytical predictions in more realistic scenarios.

The analytical model predicts catch bond behavior—a non-monotonic relationship between lifetime and force—when the probability of adhesin dissociation prior to loop opening transitions sigmoidally from 1 to 0 with increasing force. This requires the loop opening rate (rL) to be greater than the adhesin dissociation rate (rA) and the transition state distance of the loop (ΔxL) to be greater than that of the adhesin (ΔxA). The MCMC simulations show excellent agreement with the analytical predictions, confirming the existence of catch bond behavior for the chosen kinetic parameters. Four key quantities—maximum lifetime (τmax), critical force (fc), lifetime gain (τG), and normalized force range (Δf)—are defined to characterize the catch bond curves. Systematic variation of kinetic parameters reveals that the relative values of these parameters primarily govern the existence and characteristics of catch bond behavior, rather than their absolute magnitudes. The MD simulations confirm the main findings of the analytical and MCMC results, demonstrating the influence of interaction parameters (D₀, α) on the catch bond characteristics. A comparison between the analytical and MD results, establishing a relationship between kinetic and interaction parameters, shows similar trends but with minor quantitative differences attributable to nonlinearities in the energy landscape and rebinding events not explicitly modeled in the analytical theory. The influence of tether length on catch bond behavior is also investigated. It was shown that increasing tether length decreases the peak lifetime, and the catch bond behavior could be restored by re-calibrating the adhesin and loop kinetics. The authors also compare the Δf and τG values of their model with those observed in various catch bond proteins.

The study demonstrates a novel catch bond mechanism that can be implemented in polymer- or macromolecule-grafted nanoparticles. The key is controlling interface lifetime by tuning the opening kinetics of a loop, which facilitates load sharing. The analytical theory, corroborated by simulations, shows that precise control over the force-lifetime curve is possible by adjusting loop and adhesin kinetics. The ability to achieve catch bond behavior with simpler energy landscapes compared to biological systems suggests broader applicability and the potential to create synthetic catch bonds with characteristics beyond those observed in nature. The findings have implications for creating self-strengthening materials.

This research presents a versatile method for designing artificial catch bond mechanisms, suggesting that load sharing and programmed unfolding of multiple adhesion molecules might be key in generating force-enhanced lifetimes in various biomolecular systems. The ability to tailor the peak lifetime, gain, and force range of synthetic catch bonds opens up new possibilities in mechanosensitive materials, nanocomposites, and drug delivery systems. Future research could focus on investigating the mechanical properties of catch bond-capable nanoparticle networks and optimizing the design for improved performance.

The analytical model utilizes simplifications, such as Bell's theorem, which may not perfectly capture the complexity of real systems. Rebinding events, not explicitly considered in the analytical model, might influence the quantitative agreement between the analytical and simulation results. The MD simulations employ a coarse-grained representation, potentially neglecting some fine-scale details. The study focuses on a specific design and might not be fully representative of all possible designs or materials.