Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited Anisotropic Cellular Contact

Jieung Baek, Soo Yeon Cho, Hohyung Kang, Hyunah Ahn, Woo Bin Jung, Younghak Cho, Eunjung Lee, Seung-Woo Cho, Hee Tae Jung, Sung Gap Im

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Human neural stem cells (hNSCs) can alter their fate choice in response to the biophysical cues provided during development. In particular, it has been reported that the differentiation of neural stem cells (NSCs) is enhanced by anisotropic contact, which facilitates focal adhesion (FA) formation and cytoskeletal organization. However, a biomolecular mechanism governing how the cells process the biophysical cues from these anisotropic geometries to their fate commitment is still poorly understood due to the limited availability of geometrical diversities (contact width above 50 nm) applicable to cell studies. Here, we firstly demonstrate that the biomolecular mechanism for enhanced neurogenesis on an anisotropic nanostructure is critically dependent on the resolution of a contact feature. We observed a totally different cellular response to anisotropic geometries by first utilizing a high-resolution nanogroove (HRN) structure with an extremely narrow contact width (15 nm). The width scale is sufficiently low to suppress the integrin clustering and enable us to elucidate how the contact area influences the neurogenesis of hNSCs at an aligned state. Both the HRN and control nanogroove (CN) pattern with a contact width of 1 μm induced the spontaneous topographic alignment of hNSCs. However, intriguingly, the focal adhesion (FA) formation and cytoskeletal reorganization were substantially limited on the HRN, although the cells on the CN showed enhanced FA formation compared with flat surfaces. In particular, the hNSCs on the HRN surface exhibited a strikingly lower fraction of nuclear yes-associated protein (YAP) than on the CN surface, which was turned out to be regulated by Rho GTPase in the same way as the cells sense the mechanical properties of the environment. Considering the previously reported role of YAP on neurogenesis, our finding newly substantiates that YAP and Rho GTPase also can be transducers of hNSCs to process topographical alternation to fate decision. Furthermore, this study with the unprecedented high-resolution nanostructure suggests a novel geometry sensing model where the functional crosstalk between YAP signaling and Rho GTPase integrally regulate the fate commitment of the hNSCs.

Original languageEnglish
Pages (from-to)33891-33900
Number of pages10
JournalACS Applied Materials and Interfaces
Volume10
Issue number40
DOIs
Publication statusPublished - 2018 Oct 10

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Stem cells
rho GTP-Binding Proteins
Proteins
Adhesion
Geometry
Nanostructures
Control surfaces
Crosstalk
Integrins
Transducers
Availability
Mechanical properties

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

Cite this

Baek, Jieung ; Cho, Soo Yeon ; Kang, Hohyung ; Ahn, Hyunah ; Jung, Woo Bin ; Cho, Younghak ; Lee, Eunjung ; Cho, Seung-Woo ; Jung, Hee Tae ; Im, Sung Gap. / Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited Anisotropic Cellular Contact. In: ACS Applied Materials and Interfaces. 2018 ; Vol. 10, No. 40. pp. 33891-33900.
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title = "Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited Anisotropic Cellular Contact",
abstract = "Human neural stem cells (hNSCs) can alter their fate choice in response to the biophysical cues provided during development. In particular, it has been reported that the differentiation of neural stem cells (NSCs) is enhanced by anisotropic contact, which facilitates focal adhesion (FA) formation and cytoskeletal organization. However, a biomolecular mechanism governing how the cells process the biophysical cues from these anisotropic geometries to their fate commitment is still poorly understood due to the limited availability of geometrical diversities (contact width above 50 nm) applicable to cell studies. Here, we firstly demonstrate that the biomolecular mechanism for enhanced neurogenesis on an anisotropic nanostructure is critically dependent on the resolution of a contact feature. We observed a totally different cellular response to anisotropic geometries by first utilizing a high-resolution nanogroove (HRN) structure with an extremely narrow contact width (15 nm). The width scale is sufficiently low to suppress the integrin clustering and enable us to elucidate how the contact area influences the neurogenesis of hNSCs at an aligned state. Both the HRN and control nanogroove (CN) pattern with a contact width of 1 μm induced the spontaneous topographic alignment of hNSCs. However, intriguingly, the focal adhesion (FA) formation and cytoskeletal reorganization were substantially limited on the HRN, although the cells on the CN showed enhanced FA formation compared with flat surfaces. In particular, the hNSCs on the HRN surface exhibited a strikingly lower fraction of nuclear yes-associated protein (YAP) than on the CN surface, which was turned out to be regulated by Rho GTPase in the same way as the cells sense the mechanical properties of the environment. Considering the previously reported role of YAP on neurogenesis, our finding newly substantiates that YAP and Rho GTPase also can be transducers of hNSCs to process topographical alternation to fate decision. Furthermore, this study with the unprecedented high-resolution nanostructure suggests a novel geometry sensing model where the functional crosstalk between YAP signaling and Rho GTPase integrally regulate the fate commitment of the hNSCs.",
author = "Jieung Baek and Cho, {Soo Yeon} and Hohyung Kang and Hyunah Ahn and Jung, {Woo Bin} and Younghak Cho and Eunjung Lee and Seung-Woo Cho and Jung, {Hee Tae} and Im, {Sung Gap}",
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Baek, J, Cho, SY, Kang, H, Ahn, H, Jung, WB, Cho, Y, Lee, E, Cho, S-W, Jung, HT & Im, SG 2018, 'Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited Anisotropic Cellular Contact', ACS Applied Materials and Interfaces, vol. 10, no. 40, pp. 33891-33900. https://doi.org/10.1021/acsami.8b10171

Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited Anisotropic Cellular Contact. / Baek, Jieung; Cho, Soo Yeon; Kang, Hohyung; Ahn, Hyunah; Jung, Woo Bin; Cho, Younghak; Lee, Eunjung; Cho, Seung-Woo; Jung, Hee Tae; Im, Sung Gap.

In: ACS Applied Materials and Interfaces, Vol. 10, No. 40, 10.10.2018, p. 33891-33900.

Research output: Contribution to journalArticle

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T1 - Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited Anisotropic Cellular Contact

AU - Baek, Jieung

AU - Cho, Soo Yeon

AU - Kang, Hohyung

AU - Ahn, Hyunah

AU - Jung, Woo Bin

AU - Cho, Younghak

AU - Lee, Eunjung

AU - Cho, Seung-Woo

AU - Jung, Hee Tae

AU - Im, Sung Gap

PY - 2018/10/10

Y1 - 2018/10/10

N2 - Human neural stem cells (hNSCs) can alter their fate choice in response to the biophysical cues provided during development. In particular, it has been reported that the differentiation of neural stem cells (NSCs) is enhanced by anisotropic contact, which facilitates focal adhesion (FA) formation and cytoskeletal organization. However, a biomolecular mechanism governing how the cells process the biophysical cues from these anisotropic geometries to their fate commitment is still poorly understood due to the limited availability of geometrical diversities (contact width above 50 nm) applicable to cell studies. Here, we firstly demonstrate that the biomolecular mechanism for enhanced neurogenesis on an anisotropic nanostructure is critically dependent on the resolution of a contact feature. We observed a totally different cellular response to anisotropic geometries by first utilizing a high-resolution nanogroove (HRN) structure with an extremely narrow contact width (15 nm). The width scale is sufficiently low to suppress the integrin clustering and enable us to elucidate how the contact area influences the neurogenesis of hNSCs at an aligned state. Both the HRN and control nanogroove (CN) pattern with a contact width of 1 μm induced the spontaneous topographic alignment of hNSCs. However, intriguingly, the focal adhesion (FA) formation and cytoskeletal reorganization were substantially limited on the HRN, although the cells on the CN showed enhanced FA formation compared with flat surfaces. In particular, the hNSCs on the HRN surface exhibited a strikingly lower fraction of nuclear yes-associated protein (YAP) than on the CN surface, which was turned out to be regulated by Rho GTPase in the same way as the cells sense the mechanical properties of the environment. Considering the previously reported role of YAP on neurogenesis, our finding newly substantiates that YAP and Rho GTPase also can be transducers of hNSCs to process topographical alternation to fate decision. Furthermore, this study with the unprecedented high-resolution nanostructure suggests a novel geometry sensing model where the functional crosstalk between YAP signaling and Rho GTPase integrally regulate the fate commitment of the hNSCs.

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