Semiflexible polymer networks are ubiquitous in biological systems, including a scaffolding structure within cells called the actin cytoskeleton. The polymers in these networks are interconnected by transient bonds. For example, actin filaments in the cytoskeleton are physically connected via cross-linker proteins. The mechanical and kinetic properties of the cross-linkers significantly affect the rheological properties of the actin cytoskeleton. Here, we employed an agent-based model to elucidate how the force-dependent behaviors of the cross-linkers determine the material properties of passive networks without molecular motors and the force generation of active networks with molecular motors. The cross-linkers are assumed to behave either as a slip bond, whose dissociation rate increases with forces, or as a catch-slip bond, whose dissociation rate decreases with forces at low force level but increases with forces at high force level. We found that catch-slip-bond cross-linkers can simultaneously increase both the stress and the strain at the yield point. Through a systematic variation in the force dependence of the catch-slip bonds, we identified the specific parameter regimes that enable network reinforcement and enhanced extensibility simultaneously. Specifically, we found that a sufficiently large force threshold for the catch-slip transition is essential for maintaining dynamic force-bearing elements that turnover continuously—a mechanism not achievable with slip bonds. Additionally, we demonstrate that such force-dependent redistribution of the catch-slip bonds substantially enhances internal contractile forces generated by a motor in active networks. Statement of significance: Polymer networks are ubiquitous in industrial and biological systems. The polymers in these networks are often interconnected by transient bonds. The transient bonds behave as a slip bond whose dissociation rate is proportional to forces or as a catch-slip bond whose dissociation rate decreases with increased force (catch) at low force level but increases with increased force (slip) at high force level. In this study, we computationally tested different types of catch-slip bonds to define how the material properties of polymer networks are fine-tuned by each property of molecular bonds. We found that catch-slip bonds can increase both stress and strain at a yield point, which is impossible to achieve without the catch-slip bonds.

Molecular catch bonds are ubiquitous in biology and essential for processes like leucocyte extravasion¹ and cellular mechanosensing². Unlike normal (slip) bonds, catch bonds strengthen under tension. The current paradigm is that this feature provides ‘strength on demand³’, thus enabling cells to increase rigidity under stress^1,4–6. However, catch bonds are often weaker than slip bonds because they have cryptic binding sites that are usually buried^7,8. Here we show that catch bonds render reconstituted cytoskeletal actin networks stronger than slip bonds, even though the individual bonds are weaker. Simulations show that slip bonds remain trapped in stress-free areas, whereas weak binding allows catch bonds to mitigate crack initiation by moving to high-tension areas. This ‘dissociation on demand’ explains how cells combine mechanical strength with the adaptability required for shape change, and is relevant to diseases where catch bonding is compromised^7,9, including focal segmental glomerulosclerosis¹⁰ caused by the α-actinin-4 mutant studied here. We surmise that catch bonds are the key to create life-like materials.

Transiently crosslinked actin filament networks allow cells to combine elastic rigidity with the ability to deform viscoelastically. Theoretical models of semiflexible polymer networks predict that the crosslinker unbinding rate governs the timescale beyond which viscoelastic flow occurs. However a direct comparison between network and crosslinker dynamics is lacking. Here we measure the network's stress relaxation timescale using rheology and the lifetime of bound crosslinkers using fluorescence recovery after photobleaching (FRAP). Intriguingly, we observe that the crosslinker unbinding rate measured by FRAP is more than an order of magnitude slower than the rate measured by rheology. We rationalize this difference with a three-state model where crosslinkers are bound to either 0, 1 or 2 filaments, which allows us to extract crosslinker transition rates that are otherwise difficult to access. We find that the unbinding rate of singly bound crosslinkers is nearly two orders of magnitude slower than for doubly bound ones. We attribute the increased unbinding rate of doubly bound crosslinkers to the high stiffness of biopolymers, which frustrates crosslinker binding.

We study the role of a biomimetic actin network during the application of electric pulses that induce electroporation or electropermeabilization, using giant unilamellar vesicles (GUVs) as a model system. The actin cortex, a subjacently attached interconnected network of actin filaments, regulates the shape and mechanical properties of the plasma membrane of mammalian cells, and is a major factor influencing the mechanical response of the cell to external physical cues. We demonstrate that the presence of an actin shell inhibits the formation of macropores in the electroporated GUVs. Additionally, experiments on the uptake of dye molecules after electroporation show that the actin network slows down the resealing process of the permeabilized membrane. We further analyze the stability of the actin network inside the GUVs exposed to high electric pulses. We find disruption of the actin layer that is likely due to the electrophoretic forces acting on the actin filaments during the permeabilization of the GUVs. Our findings on the GUVs containing a biomimetic network provide a step towards understanding the discrepancies between the electroporation mechanism of a living cell and its simplified model of the empty GUV.