Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

48-POS Board 48 Paclitaxel Affects the Time-Dependent Response of Peripheral Nerves to Uniaxial Tensile Loading in Vitro Daniel Berrellez 1 , Carlos Luna 2 , Adam H. Hsieh 2,3 , Amir Maldonado 4 , Sameer B. Shah 5 . 1 Universidad de Sonora, Hermosillo, Sonora, Mexico, 2 University of Maryland, College Park, MD, USA, 3 University of Maryland, Baltimore, MD, USA, 4 Universidad de Sonora, Hermosillo, Sonora, Mexico, 5 University of California, San Diego, CA, USA. Paclitaxel is a common chemotherapeutic drug for the treatment of cancer; it prevents cell division by stabilizing microtubules and preventing their depolymerization. The systemic delivery of Paclitaxel causes it to accumulate in peripheral nerves leading to debilitating peripheral sensory neuropathy. The mechanisms for abnormal microtubule aggregation and neuropathy after paclitaxel treatment remain unknown. Studies suggest that alterations to microtubules can influence tensile axonal biomechanics and affect nerve function. We hypothesized that changes in the biomechanical properties of peripheral nerves may contribute to paclitaxel-induced neuropathy. In this work we explored the biomechanical changes caused by paclitaxel in mice sural nerves, sensory branches of sciatic nerves, during tensile loading and stress relaxation. Paired sural nerves from each mouse were excised and soaked in Ringer’s solution, either with or without paclitaxel. Nerves were secured between a linear actuator and a force transducer. Then, tissues were subjected to uniaxial tensile loading with a relaxation of 180 s per strain. We obtained the tensile moduli from stress vs. strain curves during equilibrium and analyzed the stress relaxation behavior with a viscoelastic model for nerves with and without paclitaxel. Our results suggest that paclitaxel stiffens nerves and reduces their stress relaxation behavior, which can be correlated with the stabilization of microtubules within axons. These data suggest that the response to strain and the time-dependent rate at which nerves can recover is affected by paclitaxel treatment and might contribute to neuropathic progression.

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