The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform
Biophysical parameters such as substrate topography and stiffness have been shown independently to elicit profound effects on neuronal differentiation and maturation from neural progenitor cells (NPCs) yet have not been investigated in combination. Here, the effects of various micrograting and stiff...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
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2023
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| Online Access: | https://hdl.handle.net/10356/169490 |
| _version_ | 1826123376044802048 |
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| author | Mattiassi, Sabrina Conner, Abigail A. Feng, Fan Goh, Eyleen Lay Keow Yim, Evelyn K. F. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Mattiassi, Sabrina Conner, Abigail A. Feng, Fan Goh, Eyleen Lay Keow Yim, Evelyn K. F. |
| author_sort | Mattiassi, Sabrina |
| collection | NTU |
| description | Biophysical parameters such as substrate topography and stiffness have been shown independently to elicit profound effects on neuronal differentiation and maturation from neural progenitor cells (NPCs) yet have not been investigated in combination. Here, the effects of various micrograting and stiffness combinations on neuronal differentiation and maturation were investigated using a polyacrylamide and N-acryloyl-6-aminocaproic acid copolymer (PAA-ACA) hydrogel with tunable stiffness. Whole laminin was conjugated onto the PAA-ACA surface indirectly or directly to facilitate long-term mouse and human NPC-derived neuron attachment. Three micrograting dimensions (2-10 µm) were patterned onto gels with varying stiffness (6.1-110.5 kPa) to evaluate the effects of topography, stiffness, and their interaction. The results demonstrate that the extracellular matrix (ECM)-modified PAA-ACA gels support mouse and human neuronal cell attachment throughout the differentiation and maturation stages (14 and 28 days, respectively). The interaction between topography and stiffness is shown to significantly increase the proportion of β-tubulin III (TUJ1) positive neurons and microtubule associated protein-2 (MAP2) positive neurite branching and length. Thus, the effects of topography and stiffness cannot be imparted. These results provide a novel platform for neural mechanobiology studies and emphasize the utility of optimizing numerous biophysical cues for improved neuronal yield in vitro. |
| first_indexed | 2024-10-01T06:03:39Z |
| format | Journal Article |
| id | ntu-10356/169490 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:03:39Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1694902023-07-23T15:38:13Z The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform Mattiassi, Sabrina Conner, Abigail A. Feng, Fan Goh, Eyleen Lay Keow Yim, Evelyn K. F. Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Neuronal Differentiation Mechanobiology Biophysical parameters such as substrate topography and stiffness have been shown independently to elicit profound effects on neuronal differentiation and maturation from neural progenitor cells (NPCs) yet have not been investigated in combination. Here, the effects of various micrograting and stiffness combinations on neuronal differentiation and maturation were investigated using a polyacrylamide and N-acryloyl-6-aminocaproic acid copolymer (PAA-ACA) hydrogel with tunable stiffness. Whole laminin was conjugated onto the PAA-ACA surface indirectly or directly to facilitate long-term mouse and human NPC-derived neuron attachment. Three micrograting dimensions (2-10 µm) were patterned onto gels with varying stiffness (6.1-110.5 kPa) to evaluate the effects of topography, stiffness, and their interaction. The results demonstrate that the extracellular matrix (ECM)-modified PAA-ACA gels support mouse and human neuronal cell attachment throughout the differentiation and maturation stages (14 and 28 days, respectively). The interaction between topography and stiffness is shown to significantly increase the proportion of β-tubulin III (TUJ1) positive neurons and microtubule associated protein-2 (MAP2) positive neurite branching and length. Thus, the effects of topography and stiffness cannot be imparted. These results provide a novel platform for neural mechanobiology studies and emphasize the utility of optimizing numerous biophysical cues for improved neuronal yield in vitro. Published version This research was funded by Natural Science and Engineering Research Council (NSERC) Discovery (2016040, RGPIN-2021-03200), the Center for Biotechnology and Bioengineering Seed Fund from the University of Waterloo and the University of Waterloo Startup Fund, and partially supported by Canada Foundation for Innovation (CFI)-John R. Evans Leaders Fund (JELF) (35573), NSERC Research Tools and Instruments (RTI-2018-00220, RTI-2020-00179). S.M. was supported by NSERC Canada Alexander Graham Bell Canada Graduate Scholarships—Master’s program and the University of Waterloo Engineering Excellence Fellowship. A.A.C., S.M. and F.F. were partially supported by NSERC CREATE (401207296). 2023-07-20T04:49:14Z 2023-07-20T04:49:14Z 2023 Journal Article Mattiassi, S., Conner, A. A., Feng, F., Goh, E. L. K. & Yim, E. K. F. (2023). The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform. Cells, 12(6), 934-. https://dx.doi.org/10.3390/cells12060934 2073-4409 https://hdl.handle.net/10356/169490 10.3390/cells12060934 36980275 2-s2.0-85151107194 6 12 934 en Cells © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). application/pdf |
| spellingShingle | Science::Medicine Neuronal Differentiation Mechanobiology Mattiassi, Sabrina Conner, Abigail A. Feng, Fan Goh, Eyleen Lay Keow Yim, Evelyn K. F. The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| title | The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| title_full | The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| title_fullStr | The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| title_full_unstemmed | The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| title_short | The combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| title_sort | combined effects of topography and stiffness on neuronal differentiation and maturation using a hydrogel platform |
| topic | Science::Medicine Neuronal Differentiation Mechanobiology |
| url | https://hdl.handle.net/10356/169490 |
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