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Mechanobiology of Disease
Poster Abstracts
115
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.