Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion

Xinyue Liu; Siyuan Rao; Weixuan Chen; Kayla Felix; Jiahua Ni; Atharva Sahasrabudhe; Shaoting Lin; Qianbin Wang; Yuanyuan Liu; Zhigang He; Jingyi Xu; Sizhe Huang; Eunji Hong; Todd Yau; Polina Anikeeva; Xuanhe Zhao

doi:10.1038/s41592-023-02020-9

Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion

Nat Methods. 2023 Nov;20(11):1802-1809. doi: 10.1038/s41592-023-02020-9. Epub 2023 Oct 19.

Authors

Xinyue Liu^#^{1

2}, Siyuan Rao^#^{3

4}, Weixuan Chen⁵, Kayla Felix⁵, Jiahua Ni⁶, Atharva Sahasrabudhe^{7

8

9}, Shaoting Lin^{6

10}, Qianbin Wang^{5

11}, Yuanyuan Liu¹², Zhigang He^{13

14}, Jingyi Xu⁵, Sizhe Huang^{5

11}, Eunji Hong^{5

11}, Todd Yau¹⁵, Polina Anikeeva^#^{16

17

18

19

20}, Xuanhe Zhao^#^{21

22}

Affiliations

¹ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. xyliu@msu.edu.
² Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA. xyliu@msu.edu.
³ Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, USA. syrao@binghamton.edu.
⁴ Department of Biomedical Engineering, Binghamton University, State University of New York, Binghamton, NY, USA. syrao@binghamton.edu.
⁵ Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, USA.
⁶ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁸ McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁰ Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA.
¹¹ Department of Biomedical Engineering, Binghamton University, State University of New York, Binghamton, NY, USA.
¹² Somatosensation and Pain Unit, National Institute of Dental and Craniofacial Research, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD, USA.
¹³ F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Neurology, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, MA, USA.
¹⁶ Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
¹⁷ McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
¹⁸ Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
¹⁹ Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
²⁰ K. Lisa Yang Brain-Body Center, Massachusetts Institute of Technology, Cambridge, MA, USA. anikeeva@mit.edu.
²¹ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhaox@mit.edu.
²² Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. zhaox@mit.edu.

^# Contributed equally.

Abstract

We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm^-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.

MeSH terms

Animals
Hydrogels
Locomotion
Mice
Motor Activity
Optical Fibers*
Optogenetics*
Sciatic Nerve / physiology

Substances

Hydrogels

Abstract

MeSH terms

Substances

Grants and funding