TY - JOUR
T1 - Probing for chemotherapy-induced peripheral neuropathy in live dorsal root ganglion neurons with atomic force microscopy
AU - Au, Ngan Pan Bennett
AU - Fang, Yuqiang
AU - Xi, Ning
AU - Lai, King Wai Chiu
AU - Ma, Chi Him Eddie
N1 - Funding Information:
This work is supported in part by an ECS/GRF grant from the Research Grant Council of the Hong Kong Special Administrative Region Government ( CityU 161212 and CityU 160813 ), The Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong Special Administrative Region Government (01122016 and 01122026), Centre for Biosystems, Neuroscience, and Nanotechnology at City University of Hong Kong and the City University of Hong Kong Seed Funding ( 7003028 ) award to Chi Ma; an ECS/GRF grant from the Research Grant Council of the Hong Kong Special Administrative Region Government ( CityU 139313 ), Centre for Robotics and Automation at City University of Hong Kong , the City University of Hong Kong Startup Fund ( 7200311 and 9610254 ) and Seed Funding ( 7003018 ) award to King Lai; and an GRF grant from the Research Grant Council of the Hong Kong Special Administrative Region Government (CityU 124213) and the City University of Hong Kong Startup Fund ( 7002841 ) award to Ning Xi.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - Chemotherapy-induced peripheral neuropathy (CIPN) remains a major reason for cancer patients to withdraw from their lifesaving therapy. CIPN results in irreversible sensory and motor impairments; however, the epidemiology is largely unknown. Here, we report for the first time that chemotherapy drug vincristine not only reduced axonal regeneration in primary dorsal root ganglion neuron but also induced substantial changes in cell mechanical properties detected by atomic force microscopy (AFM). Confocal imaging analysis revealed vincristine-induced microtubule depolymerization. By using AFM for high-resolution live cell imaging and quantitative analysis, we observed significant changes in cell surface roughness and stiffness of vincristine-treated neurons. Elastic modulus was decreased (21-45%) with increasing dosage of vincristine. Further study with paclitaxel, another well-known CIPN drug, confirmed the link between cell mechanics and cytoskeleton organization. These data support that our system can be used for probing potential CIPN drugs that are of enormous benefit to new chemotherapy drug development. From the Clinical Editor: This study concludes that reduced cell elasticity in dorsal root ganglion neurons accompanies the development of chemotherapy-induced peripheral neuropathy, providing a model system that enables testing of upcoming chemotherapy agents for this particularly inconvenient and often treatment-limiting complication.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) remains a major reason for cancer patients to withdraw from their lifesaving therapy. CIPN results in irreversible sensory and motor impairments; however, the epidemiology is largely unknown. Here, we report for the first time that chemotherapy drug vincristine not only reduced axonal regeneration in primary dorsal root ganglion neuron but also induced substantial changes in cell mechanical properties detected by atomic force microscopy (AFM). Confocal imaging analysis revealed vincristine-induced microtubule depolymerization. By using AFM for high-resolution live cell imaging and quantitative analysis, we observed significant changes in cell surface roughness and stiffness of vincristine-treated neurons. Elastic modulus was decreased (21-45%) with increasing dosage of vincristine. Further study with paclitaxel, another well-known CIPN drug, confirmed the link between cell mechanics and cytoskeleton organization. These data support that our system can be used for probing potential CIPN drugs that are of enormous benefit to new chemotherapy drug development. From the Clinical Editor: This study concludes that reduced cell elasticity in dorsal root ganglion neurons accompanies the development of chemotherapy-induced peripheral neuropathy, providing a model system that enables testing of upcoming chemotherapy agents for this particularly inconvenient and often treatment-limiting complication.
KW - AFM live cell imaging
KW - cell mechanic
KW - chemotherapy-induced peripheral neuropathy
KW - dorsal root ganglion neurons
KW - nanoindentation
UR - http://www.scopus.com/inward/record.url?scp=84905232719&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2014.03.002
DO - 10.1016/j.nano.2014.03.002
M3 - Article
C2 - 24632247
AN - SCOPUS:84905232719
SN - 1549-9634
VL - 10
SP - 1323
EP - 1333
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 6
ER -