Journal article
Microtopographical features generated by photopolymerization recruit RhoA/ROCK through TRPV1 to direct cell and neurite growth
Biomaterials, Vol.53, pp.95-106
06/2015
DOI: 10.1016/j.biomaterials.2015.02.057
PMCID: PMC4405664
PMID: 25890710
Abstract
Cell processes, including growth cones, respond to biophysical cues in their microenvironment to establish functional tissue architecture and intercellular networks. The mechanisms by which cells sense and translate biophysical cues into directed growth are unknown. We used photopolymerization to fabricate methacrylate platforms with patterned microtopographical features that precisely guide neurite growth and Schwann cell alignment. Pharmacologic inhibition of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or reduced expression of TRPV1 by RNAi significantly disrupts neurite guidance by these microtopographical features. Exogenous expression of TRPV1 induces alignment of NIH3T3 fibroblasts that fail to align in the absence of TRPV1, further implicating TRPV1 channels as critical mediators of cellular responses to biophysical cues. Microtopographic features increase RhoA activity in growth cones and in TRPV1-expressing NIH3T3 cells. Further, Rho-associated kinase (ROCK) phosphorylation is elevated in growth cones and neurites on micropatterned surfaces. Inhibition of RhoA/ROCK by pharmacological compounds or reduced expression of either ROCKI or ROCKII isoforms by RNAi abolishes neurite and cell alignment, confirming that RhoA/ROCK signaling mediates neurite and cell alignment to microtopographic features. These studies demonstrate that microtopographical cues recruit TRPV1 channels and downstream signaling pathways, including RhoA and ROCK, to direct neurite and cell growth.
Details
- Title: Subtitle
- Microtopographical features generated by photopolymerization recruit RhoA/ROCK through TRPV1 to direct cell and neurite growth
- Creators
- Shufeng Li - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USABradley W Tuft - Department of Chemical and Biochemical Engineering, University of Iowa, Iowa City, IA 52242, USALinjing Xu - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAMarc A Polacco - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAJoseph C Clarke - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAC. Allan Guymon - Department of Chemical and Biochemical Engineering, University of Iowa, Iowa City, IA 52242, USAMarlan R Hansen - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Biomaterials, Vol.53, pp.95-106
- DOI
- 10.1016/j.biomaterials.2015.02.057
- PMID
- 25890710
- PMCID
- PMC4405664
- NLM abbreviation
- Biomaterials
- ISSN
- 0142-9612
- eISSN
- 1878-5905
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000055, name: NIDCD, award: R01 DC012578, P30 DC010362; DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: NSFC 81171482; name: Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship
- Language
- English
- Date published
- 06/2015
- Academic Unit
- Molecular Physiology and Biophysics; Chemical and Biochemical Engineering; Neurosurgery; Otolaryngology
- Record Identifier
- 9984007162902771
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