19 research outputs found

    A Unified Framework for Hopsets

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    Given an undirected graph G = (V,E), an (?,?)-hopset is a graph H = (V,E\u27), so that adding its edges to G guarantees every pair has an ?-approximate shortest path that has at most ? edges (hops), that is, d_G(u,v) ? d_{G?H}^(?)(u,v) ? ?? d_G(u,v). Given the usefulness of hopsets for fundamental algorithmic tasks, several different algorithms and techniques were developed for their construction, for various regimes of the stretch parameter ?. In this work we devise a single algorithm that can attain all state-of-the-art hopsets for general graphs, by choosing the appropriate input parameters. In fact, in some cases it also improves upon the previous best results. We also show a lower bound on our algorithm. In [Ben-Levy and Parter, 2020], given a parameter k, a (O(k^?),O(k^{1-?}))-hopset of size O?(n^{1+1/k}) was shown for any n-vertex graph and parameter 0 < ? < 1, and they asked whether this result is best possible. We resolve this open problem, showing that any (?,?)-hopset of size O(n^{1+1/k}) must have ??? ? ?(k)

    Origins of Activity Enhancement in Enzyme Cascades on Scaffolds

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    The concept of “metabolic channeling” as a result of rapid transfer of freely diffusing intermediate substrates between two enzymes on nanoscale scaffolds is examined using simulations and mathematical models. The increase in direct substrate transfer due to the proximity of the two enzymes provides an initial but temporary boost to the throughput of the cascade and loses importance as product molecules of enzyme 1 (substrate molecules of enzyme 2) accumulate in the surrounding container. The characteristic time scale at which this boost is significant is given by the ratio of container volume to the product of substrate diffusion constant and interenzyme distance and is on the order of milliseconds to seconds in some experimental systems. However, the attachment of a large number of enzyme pairs to a scaffold provides an increased number of local “targets”, extending the characteristic time. If substrate molecules for enzyme 2 are sequestered by an alternative reaction in the container, a scaffold can result in a permanent boost to cascade throughput with a magnitude given by the ratio of the above-defined time scale to the lifetime of the substrate molecule in the container. Finally, a weak attractive interaction between substrate molecules and the scaffold creates a “virtual compartment” and substantially accelerates initial throughput. If intermediate substrates can diffuse freely, placing individual enzyme pairs on scaffolds is only beneficial in large cells, unconfined extracellular spaces or in systems with sequestering reactions

    Velocity Fluctuations in Kinesin‑1 Gliding Motility Assays Originate in Motor Attachment Geometry Variations

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    Motor proteins such as myosin and kinesin play a major role in cellular cargo transport, muscle contraction, cell division, and engineered nanodevices. Quantifying the collective behavior of coupled motors is critical to our understanding of these systems. An excellent model system is the gliding motility assay, where hundreds of surface-adhered motors propel one cytoskeletal filament such as an actin filament or a microtubule. The filament motion can be observed using fluorescence microscopy, revealing fluctuations in gliding velocity. These velocity fluctuations have been previously quantified by a motional diffusion coefficient, which Sekimoto and Tawada explained as arising from the addition and removal of motors from the linear array of motors propelling the filament as it advances, assuming that different motors are not equally efficient in their force generation. A computational model of kinesin head diffusion and binding to the microtubule allowed us to quantify the heterogeneity of motor efficiency arising from the combination of anharmonic tail stiffness and varying attachment geometries assuming random motor locations on the surface and an absence of coordination between motors. Knowledge of the heterogeneity allows the calculation of the proportionality constant between the motional diffusion coefficient and the motor density. The calculated value (0.3) is within a standard error of our measurements of the motional diffusion coefficient on surfaces with varying motor densities calibrated by landing rate experiments. This allowed us to quantify the loss in efficiency of coupled molecular motors arising from heterogeneity in the attachment geometry
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