Size-Tunable Nanoneedle Arrays for Influencing Stem Cell Morphology, Gene Expression, and Nuclear Membrane Curvature

Hyejeong Seong, Stuart Higgins, Jelle Penders, James Armstrong, Spencer Crowder, Axel Moore, Julia Sero, Michele Becce, Molly Stevens

Research output: Contribution to journalArticlepeer-review

60 Citations (SciVal)

Abstract

High-aspect-ratio nanostructures have emerged as versatile platforms for intracellular sensing and biomolecule delivery. Here, we present a microfabrication approach in which a combination of reactive ion etching protocols were used to produce high-aspect-ratio, nondegradable silicon nanoneedle arrays with tip diameters that could be finely tuned between 20 and 700 nm. We used these arrays to guide the long-term culture of human mesenchymal stem cells (hMSCs). Notably, we used changes in the nanoneedle tip diameter to control the morphology, nuclear size, and F-actin alignment of interfaced hMSCs and to regulate the expression of nuclear lamina genes, Yes-associated protein (YAP) target genes, and focal adhesion genes. These topography-driven changes were attributed to signaling by Rho-family GTPase pathways, differences in the effective stiffness of the nanoneedle arrays, and the degree of nuclear membrane impingement, with the latter clearly visualized using focused ion beam scanning electron microscopy (FIB-SEM). Our approach to design high-aspect-ratio nanostructures will be broadly applicable to design biomaterials and biomedical devices used for long-term cell stimulation and monitoring.
Original languageEnglish
Pages (from-to)5371–5381
Number of pages11
JournalACS Nano
Volume14
Issue number5
Early online date24 Apr 2020
DOIs
Publication statusPublished - 26 May 2020

Funding

H.S. was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A03007397) and the European Commission (H2020-MSCA-IF-2017, 797311). H.S., J.E,S. and M.M.S. acknowledge support from the Engineering and Physical Sciences Research Council (EPSRC) programme grant "Advanced Functional Materials" (EP/M020398/1). S.G.H. and M.M.S. acknowledge funding from the EU Framework Programme 7 project “Naturale CG” (grant number 616417). J.P. acknowledges funding from the NanoMed Marie Skłodowska-Curie ITN from the H2020 program (676137). J.P.K.A. was funded by Arthritis Research U.K. (21138) and the Medical Research Council (MR/S00551X/1). A.C.M. was supported by the Whitaker International Program, Institute of International Education. A.C.M. and M.M.S. acknowledge the grant from the UK Regenerative Medicine Platform “Acellular/Smart Materials–3D Architecture” (MR/R015651/1). M.B. and M.M.S. acknowledge funding from the Rosetrees Trust. M.M.S. acknowledges a Wellcome Trust Senior Investigator Award (098411/Z/12/Z). The authors acknowledge the Facility for Imaging by Light Microscopy (FILM) at Imperial College London (financially supported by Wellcome Trust funding, grant 104931/Z/14/Z) and technical support from the London Centre of Nanotechnology (LCN), Ms. Melisse Chee, Ms. Charlotte Lee-Reeves, and Dr. Akemi Nogiwa Valdez.

Keywords

  • nanotechnology
  • cell morphology
  • stem cells

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