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Nanoscale Patterning of Extracellular Matrix Alters Endothelial Function under Shear Stress Public Deposited

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Supporting information is available online at:  http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.5b04028

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  • The role of nanotopographical extracellular matrix (ECM) cues in vascular endothelial cell (EC) organization and function is not well-understood, despite the composition of nano- to microscale fibrillar ECMs within blood vessels. Instead, the predominant modulator of EC organization and function is traditionally thought to be hemodynamic shear stress, in which uniform shear stress induces parallel-alignment of ECs with anti-inflammatory function, whereas disturbed flow induces a disorganized configuration with pro-inflammatory function. Since shear stress acts on ECs by applying a mechanical force concomitant with inducing spatial patterning of the cells, we sought to decouple the effects of shear stress using parallel-aligned nanofibrillar collagen films that induce parallel EC alignment prior to stimulation with disturbed flow resulting from spatial wall shear stress gradients. Using real time live-cell imaging, we tracked the alignment, migration trajectories, proliferation, and anti-inflammatory behavior of ECs when they were cultured on parallel-aligned or randomly oriented nanofibrillar films. Intriguingly, ECs cultured on aligned nanofibrillar films remained well-aligned and migrated predominantly along the direction of aligned nanofibrils, despite exposure to shear stress orthogonal to the direction of the aligned nanofibrils. Furthermore, in stark contrast to ECs cultured on randomly oriented films, ECs on aligned nanofibrillar films exposed to disturbed flow had significantly reduced inflammation and proliferation, while maintaining intact intercellular junctions. This work reveals fundamental insights into the importance of nanoscale ECM interactions in the maintenance of endothelial function. Importantly, it provides new insight into how ECs respond to opposing cues derived from nanotopography and mechanical shear force and has strong implications in the design of polymeric conduits and bioengineered tissues.
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  • Nakayama, K. H., Surya, V. V., Gole, M., Walker, T., Yang, W., Lai, E., ... & Huang, N. F. (2016). Nanoscale patterning of extracellular matrix alters endothelial function under shear stress. Nano Letters, 16(1), 410-419. doi:10.1021/acs.nanolett.5b04028
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  • 16
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  • This study was supported in part by grants to NFH from the U.S. National Institutes of Health (R00HL098688 and EB020235-01), Merit Review Award (1I01BX002310) from the Department of Veterans Affairs Biomedical Laboratory Research and Development, the Stanford Chemistry Engineering and Medicine for Human Health, and the Stanford Cardiovascular Institute. This study was supported in part by a grant to ARD and GGF from the National Institutes of Health (R01HL128779-01). K.H.N. was supported by postdoctoral fellowships from the National Institutes of Health (1T32HL098049) and the American Heart Association (15POST25560045).
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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2016-02-24T16:31:15Z (GMT) No. of bitstreams: 2 krauserp191151237.zip: 9941 bytes, checksum: fc64ae97e3fd5e9ab04c20630e53dbce (MD5) COP.docx: 11285 bytes, checksum: 95fc385e0874cb5a75d0997d07310135 (MD5)
  • description.provenance : Submitted by Open Access (openaccess@library.oregonstate.edu) on 2016-02-24T14:51:28Z No. of bitstreams: 1 COP.docx: 11285 bytes, checksum: 95fc385e0874cb5a75d0997d07310135 (MD5)
  • description.provenance : Made available in DSpace on 2016-02-24T16:31:15Z (GMT). No. of bitstreams: 2 krauserp191151237.zip: 9941 bytes, checksum: fc64ae97e3fd5e9ab04c20630e53dbce (MD5) COP.docx: 11285 bytes, checksum: 95fc385e0874cb5a75d0997d07310135 (MD5) Previous issue date: 2016-01

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