Korabel, N. | Search bioRxiv

bioRxiv2018

A cumulative inertia phenomenon explains anomalous long-distance transport in eukaryotic cells

We demonstrate the phenomenon of cumulative inertia in intracellular transport involving multiple motor proteins in human epithelial cells by measuring the empirical survival probability of cargoes on the microtubule and their detachment rates. We found the longer a cargo moves along a microtubule, the less likely it detaches from it. As a result, the movement of cargoes is non-Markovian and involves a memory. We observe memory effects on the scale of up to 2 seconds. We provide a theoretical link between the measured detachment rate and the super-diffusive Levy walk-like cargo movement.

biophysics↗

bioRxiv2018

An In Silico Model of DNA Repair for Investigation of Mechanisms in Non-Homologous End Joining

In human cells, non-homologous end joining is the preferred process to repair radiation induced DNA double strand breaks. The complex nature of such biological systems involves many individual actions that combine to produce an overall behaviour. As such, experimentally determining the mechanisms involved, their individual roles, and how they interact is challenging. An in silico approach to radiobiology is uniquely suited for detailed exploration of these complex interactions and the unknown effects of specific mechanisms on overall behaviour. We detail the construction of a mechanistic model by combination of several, experimentally supported, hypothesised mechanisms. Compatibility of these mechanisms was tested by fitting to results reported in the literature. To avoid over fitting, individual mechanisms within this pathway were sequentially fitted. We demonstrate that using this approach the model is capable of reproducing published protein kinetics and overall repair trends. This process highlighted specific biological mechanisms which are not clearly defined experimentally, and showed that the assumed motion of individual double strand break ends plays a crucial role in determining overall system behaviour.

systems biology↗