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Despite their importance for the proper function of living cells, the physical properties of cross-linked actin networks remain poorly understood as the occurrence of heterogeneities hamper a quantitative physical description. The isotropic homogeneously cross-linked actin network presented here enables us to quantitatively relate the network response to a single filament model by determining the dominating length scale. The frequency dependence of the linear response and nonuniversal form of the nonlinear response reveal the importance of cross-linker unbinding events.

Soluble oligomeric aggregates of alpha-synuclein have been implicated to play a central role in the pathogenesis of Parkinson's disease. Disruption and permeabilization of lipid bilayers by alpha-synuclein oligomers is postulated as a toxic mechanism, but the molecular details controlling the oligomer-membrane interaction are still unknown. Here we show that membrane disruption strongly depends on the accessibility of the hydrophobic membrane core and that charge interactions play an important but complex role. We systematically studied the influence of the physical membrane properties and solution conditions on lipid bilayer disruption by oligomers using a dye release assay. Varying the lipid headgroup composition revealed that membrane disruption only occurs for negatively charged bilayers. Furthermore, the electrostatic repulsion between the negatively charged alpha-synuclein and the negative surface charge of the bilayer inhibits vesicle disruption at low ionic strength. The disruption of negatively charged vesicles further depends on lipid packing parameters. Bilayer composition changes that result in an increased lipid headgroup spacing make vesicles more prone to disruption, suggesting that the accessibility of the bilayer hydrocarbon core modulates oligomer-membrane interaction. These data shed important new insights into the driving forces governing the highly debated process of oligomer-membrane interactions.

In contrast with entangled actin solutions, transiently cross-linked actin networks can provide highly elastic properties while still allowing for local rearrangements in the microstructure-on biological relevant time scales. Here, we show that thermal unbinding of transient cross-links entails local stress relaxation and energy dissipation in an intermediate elasticity dominated frequency regime. We quantify the viscoelastic response of an isotropically cross-linked actin network by experimentally tuning the off rate of the transiently cross-linking molecules, their density, and the solvent viscosity. We reproduce the measured frequency response by a semiphenomenological model that is predicated on microscopic unbinding events.