Label-free Multiscale Transport Imaging of the Living Cell.

The living cell is characterized by a myriad of parallel intracellular transport processes. Simultaneously capturing their global features across multiple temporal and spatial scales is a nearly unsurmountable task. Here we present a method that enables the microscopic imaging of the entire spectrum of intracellular transport on a broad time scale without the need for prior labeling.

Plasmin-driven fibrinolysis in a quasi-two-dimensional nanoscale fibrin matrix.

Fibrin plays a fundamentally important role during hemostasis. To withstand the shear forces of blood flow and prevent embolisation, fibrin monomers form a three-dimensional polymer network that serves as an elastic scaffold for the blood clot. The complex spatial hierarchy of the fibrin meshwork, however, severely complicates the exploration of structural features, mechanical properties and molecular changes associated with the individual fibers of the clot.

Topology of interaction between titin and myosin thick filaments.

Titin is a giant protein spanning between the Z- and M-lines of the sarcomere. In the A-band titin is associated with the myosin thick filament. It has been speculated that titin may serve as a blueprint for thick-filament formation due to the super-repeat structure of its A-band domains.

Dispersion and stabilization of cochleate nanoparticles.

Cochleates, calcium-stabilized membrane rolls of nanoscale diameter, promise a unique and efficient way of delivering lipid-soluble drugs, proteins or nucleic acids into biological systems because they protect the encapsulated material against enzymatic or chemical degradation. Self-aggregation, which typically arises during production and storage is a major obstacle that has so far precluded the development of an efficient cochleate-based drug-delivery system. Here we show that citric acid, added transiently in a narrow concentration range, effectively disperses cochleate aggregates, stabilizes the disperse state for long-term storage and preserves the canonical ultrastructure and topological characteristics of cochleate nanoparticles.

Optical Trapping Nanometry of Hypermethylated CPG-Island DNA.

Cytosine methylation is a key mechanism of epigenetic regulation. CpG-dense loci, called "CpG islands", play a particularly important role in modulating gene expression. Methylation has long been suspected to alter the physical properties of DNA, but the full spectrum of the evoked changes is unknown.

Titin domains progressively unfolded by force are homogenously distributed along the molecule.

Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a paradoxical violation of mechanically driven activation kinetics, neither the global domain unfolding rate, nor the folded-state lifetime distributions of full-length titin are sensitive to force.

Structural and nanomechanical comparison of epitaxially and solution-grown amyloid β25-35 fibrils.

Aβ25-35, the fibril-forming, biologically active toxic fragment of the full-length amyloid β-peptide also forms fibrils on mica by an epitaxial assembly mechanism. Here we investigated, by using atomic force microscopy, nanomechanical manipulation and FTIR spectroscopy, whether the epitaxially grown fibrils display structural and mechanical features similar to the ones evolving under equilibrium conditions in bulk solution. Unlike epitaxially grown fibrils, solution-grown fibrils displayed a heterogeneous morphology and an apparently helical structure.

Epitaxial assembly dynamics of mutant amyloid β25-35_N27C fibrils explored with time-resolved scanning force microscopy.

Amyloid β25-35 (Aβ25-35) is a toxic fragment of Alzheimer's beta peptide. We have previously shown that Aβ25-35 fibrils form a trigonally oriented network on mica by epitaxial growth mechanisms. Chemical reactivity can be furnished to the fibril by introducing a cysteine residue (Aβ25-35_N27C) while maintaining oriented assembly properties.