Dynamically modulated core-shell microfibers to study the effect of depth sensing of matrix stiffness on stem cell fate

Wei, D., Charlton, L., Glidle, A., Qi, N., Dobson, P. S. , Dalby, M. J. , Fan, H. and Yin, H. (2021) Dynamically modulated core-shell microfibers to study the effect of depth sensing of matrix stiffness on stem cell fate. ACS Applied Materials and Interfaces, 13(32), pp. 37997-38006. (doi: 10.1021/acsami.1c06752) (PMID:34355561)

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Abstract

It is well known that extracellular matrix stiffness can affect cell fate and change dynamically during many biological processes. Existing experimental means for in situ matrix stiffness modulation often alters its structure, which could induce additional undesirable effects on cells. Inspired by the phenomenon of depth sensing by cells, we introduce here core–shell microfibers with a thin collagen core for cell growth and an alginate shell that can be dynamically stiffened to deliver mechanical stimuli. This allows for the maintenance of biochemical properties and structure of the surrounding microenvironment, while dynamically modulating the effective modulus “felt” by cells. We show that simple addition of Sr2+ in media can easily increase the stiffness of initially Ca2+ cross-linked alginate shells. Thus, despite the low stiffness of collagen cores (<5 kPa), the effective modulus of the matrix “felt” by cells are substantially higher, which promotes osteogenesis differentiation of human mesenchymal stem cells. We show this effect is more prominent in the stiffening microfiber compared to a static microfiber control. This approach provides a versatile platform to independently and dynamically modulate cellular microenvironments with desirable biochemical, physical, and mechanical stimuli without an unintended interplay of effects, facilitating investigations of a wide range of dynamic cellular processes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yin, Professor Huabing and Dalby, Professor Matthew and Wei, Dan and Charlton, Ms Laura and Glidle, Dr Andrew and Dobson, Dr Phil
Creator Roles:
Wei, D.Conceptualization, Methodology, Investigation, Validation, Data curation, Formal analysis, Writing – original draft, Writing – review and editing, Visualization
Charlton, L.Conceptualization, Methodology, Investigation, Data curation
Glidle, A.Methodology, Writing – review and editing
Dobson, P. S.Methodology, Writing – review and editing
Dalby, M. J.Methodology, Writing – review and editing
Yin, H.Conceptualization, Methodology, Validation, Formal analysis, Writing – original draft, Writing – review and editing, Visualization, Resources, Funding acquisition
Authors: Wei, D., Charlton, L., Glidle, A., Qi, N., Dobson, P. S., Dalby, M. J., Fan, H., and Yin, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Engineering > Biomedical Engineering
College of Science and Engineering > School of Engineering > Electronics and Nanoscale Engineering
Journal Name:ACS Applied Materials and Interfaces
Publisher:American Chemical Society
ISSN:1944-8244
ISSN (Online):1944-8252
Published Online:06 August 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in ACS Applied Materials and Interfaces 13(32): 37997-38006
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172141EPSRC Centre for Multiscale soft tissue mechanics with application to heart & cancerRaymond OgdenEngineering and Physical Sciences Research Council (EPSRC)EP/N014642/1M&S - Mathematics
302784Extending AFM to measure and control temperature in biologically relevant environmentsPhil DobsonBiotechnology and Biological Sciences Research Council (BBSRC)BB/R021953/1ENG - Electronics & Nanoscale Engineering