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Korten, T.

Publications and source records attributed to Korten, T..

2 recordsLinked to original sources

Practically Error-Free Junctions Enable Solving Large Instances of Exact Cover Problems Using Network-Based Biocomputation

Network-based biocomputing (NBC) presents an energy-efficient, parallel computing approach for solving nondeterministic polynomial time (NP) complete problems by leveraging motor-driven cytoskeletal filaments that explore all possible solutions through nanofabricated networks in a massively parallel fashion. However, guiding errors at pass junctions, where filaments deviate from their intended path, currently limit the scalability of NBC systems. In this study, we addressed this critical challenge by fabricating sub-200 nm channel geometries using modified electron-beam-lithography and reactive-ion-etching protocols to physically constrain the trajectories of kinesin-driven microtubules and enhance path fidelity. Investigating junction designs with varying channel widths, we demonstrate that reducing channel width significantly lowers junction error rates. Practically error-free junction performance was achieved by scaling down the entire network geometry by a factor of two. These optimized junctions were incorporated into NBC networks that successfully solved 24- and 25-set instances of the Exact Cover problem, representing solution spaces of approximately 16 million and 33 million, respectively. This work establishes a new benchmark in NBC performance and represents a computational scale far beyond what has been achieved in prior demonstrations.

bioengineering↗

Microtubule lattice defects facilitate spastin-mediated severing

The length regulation of microtubules and their organization into complex arrays inside cells occurs through the activity of polymerases, depolymerases as well as severing enzymes such as katanin and spastin. The latter hexamerize on the microtubule lattice, pull out single tubulin dimers in an ATP-dependent manner and eventually generate internal breaks in the microtubule. While both, katanin and spastin, were shown to be regulated by posttranslational tubulin modifications, only katanin was reported to have microtubule lattice-defect- or crossover-sensing activity. Here, we employ in vitro assays to investigate the impact of microtubule lattice defects on the severing characteristics of spastin. Toward this end, we prepared GMPCPP-stabilized microtubules with varying defect densities. Thereby, microtubule defects were introduced either through specific polymerization conditions or by end-to-end annealing of microtubules. We found that (i) the presence of defects accelerated the onset of the severing process and (ii) severing was twice as frequent in microtubule segments with defect sites as compared to random lattice segments. However, there was no evidence of preferential binding of spastin to defect sites. We therefore propose a severing mechanism in which defects do not actively promote microtubule severing but rather passively contribute to microtubule lattice instability, facilitating the process as fewer tubulin subunits are required to be removed for microtubule severing.

biophysics↗