PMID- 25311684 OWN - NLM STAT- MEDLINE DCOM- 20150408 LR - 20230720 IS - 1878-7568 (Electronic) IS - 1742-7061 (Print) IS - 1742-7061 (Linking) VI - 12 DP - 2015 Jan TI - Biomimetic stochastic topography and electric fields synergistically enhance directional migration of corneal epithelial cells in a MMP-3-dependent manner. PG - 102-112 LID - S1742-7061(14)00449-8 [pii] LID - 10.1016/j.actbio.2014.10.007 [doi] AB - Directed migration of corneal epithelial cells (CECs) is critical for maintenance of corneal homeostasis as well as wound healing. Soluble cytoactive factors and the intrinsic chemical attributes of the underlying extracellular matrix (ECM) participate in stimulating and directing migration. The central importance of the intrinsic biophysical attributes of the microenvironment of the cell in modulating an array of fundamental epithelial behaviors including migration has been widely documented. Among the best measures of these attributes are the intrinsic topography and stiffness of the ECM and electric fields (EFs). How cells integrate these multiple simultaneous inputs is not well understood. Here, we present a method that combines the use of (i) topographically patterned substrates (mean pore diameter 800nm) possessing features that approximate those found in the native corneal basement membrane; and (ii) EFs (0-150mVmm(-1)) mimicking those at corneal epithelial wounds that the cells experience in vivo. We found that topographic cues and EFs synergistically regulated directional migration of human CECs and that this was associated with upregulation of matrix metalloproteinase-3 (MMP3). MMP3 expression and activity were significantly elevated with 150mVmm(-1) applied-EF while MMP2/9 remained unaltered. MMP3 expression was elevated in cells cultured on patterned surfaces against planar surfaces. The highest single-cell migration rate was observed with 150mVmm(-1) applied EF on patterned and planar surfaces. When cultured as a confluent sheet, EFs induced collective cell migration on stochastically patterned surfaces compared with dissociated single-cell migration on planar surfaces. These results suggest significant interaction of biophysical cues in regulating cell behaviors and will help define design parameters for corneal prosthetics and help to better understand corneal wound healing. CI - Copyright (c) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - Gao, Jing AU - Gao J AD - Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; School of Life Science, Yunnan Normal University, Kunming, Yunnan 650500, People's Republic of China. FAU - Raghunathan, Vijay Krishna AU - Raghunathan VK AD - Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA. FAU - Reid, Brian AU - Reid B AD - Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA 95817, USA. FAU - Wei, Dongguang AU - Wei D AD - Department of Otolaryngology, School of Medicine, University of California Davis, Sacramento, CA 95817, USA. FAU - Diaz, Rodney C AU - Diaz RC AD - Department of Otolaryngology, School of Medicine, University of California Davis, Sacramento, CA 95817, USA. FAU - Russell, Paul AU - Russell P AD - Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA. FAU - Murphy, Christopher J AU - Murphy CJ AD - Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA; Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Sacramento, CA 95817, USA. Electronic address: cjmurphy@ucdavis.edu. FAU - Zhao, Min AU - Zhao M AD - Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA 95817, USA; School of Life Science, Yunnan Normal University, Kunming, Yunnan 650500, People's Republic of China; Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Sacramento, CA 95817, USA. Electronic address: minzhao@ucdavis.edu. LA - eng GR - P30 EY12576/EY/NEI NIH HHS/United States GR - R01 EY019101/EY/NEI NIH HHS/United States GR - P30 EY012576/EY/NEI NIH HHS/United States GR - R01 EY012253/EY/NEI NIH HHS/United States GR - 1R01EY019101/EY/NEI NIH HHS/United States GR - R01EY016134,/EY/NEI NIH HHS/United States GR - R01 EY016134/EY/NEI NIH HHS/United States GR - R01 EY019970/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20141013 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - *Biomimetics MH - *Cell Movement MH - Epithelium, Corneal/*cytology MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Real-Time Polymerase Chain Reaction MH - *Stochastic Processes PMC - PMC4798428 MID - NIHMS636655 OTO - NOTNLM OT - Basement membrane OT - Cornea OT - Corneal epithelial cells OT - Electric field OT - Topography EDAT- 2014/10/15 06:00 MHDA- 2015/04/09 06:00 PMCR- 2016/03/18 CRDT- 2014/10/15 06:00 PHST- 2014/06/09 00:00 [received] PHST- 2014/10/02 00:00 [revised] PHST- 2014/10/04 00:00 [accepted] PHST- 2014/10/15 06:00 [entrez] PHST- 2014/10/15 06:00 [pubmed] PHST- 2015/04/09 06:00 [medline] PHST- 2016/03/18 00:00 [pmc-release] AID - S1742-7061(14)00449-8 [pii] AID - 10.1016/j.actbio.2014.10.007 [doi] PST - ppublish SO - Acta Biomater. 2015 Jan;12:102-112. doi: 10.1016/j.actbio.2014.10.007. Epub 2014 Oct 13.