Impact of type-1 collagen hydrogel density on integrin-linked morphogenic response of SH-SY5Y neuronal cells.

Autor:	Merryweather D; Department of Chemistry, Loughborough University Leicestershire LE11 3TU UK p.roach@lboro.ac.uk., Moxon SR; Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre Manchester M13 9PL UK., Capel AJ; National Centre for Sport and Exercise Medicine (NCSEM), School of Sport, Exercise and Health Sciences, Loughborough University Leicestershire LE11 3TU UK., Hooper NM; Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre Manchester M13 9PL UK., Lewis MP; National Centre for Sport and Exercise Medicine (NCSEM), School of Sport, Exercise and Health Sciences, Loughborough University Leicestershire LE11 3TU UK., Roach P; Department of Chemistry, Loughborough University Leicestershire LE11 3TU UK p.roach@lboro.ac.uk.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2021 Oct 07; Vol. 11 (52), pp. 33124-33135. Date of Electronic Publication: 2021 Oct 07 (Print Publication: 2021).
DOI:	10.1039/d1ra05257h
Abstrakt:	Cellular metabolism and behaviour is closely linked to cytoskeletal tension and scaffold mechanics. In the developing nervous system functional connectivity is controlled by the interplay between chemical and mechanical cues that initiate programs of cell behaviour. Replication of functional connectivity in neuronal populations in vitro has proven a technical challenge due to the absence of many systems of biomechanical regulation that control directional outgrowth in vivo . Here, a 3D culture system is explored by dilution of a type I collagen hydrogel to produce variation in gel stiffness. Hydrogel scaffold remodelling was found to be linked to gel collagen concentration, with a greater degree of gel contraction occurring at lower concentrations. Gel mechanics were found to evolve over the culture period according to collagen concentration. Less concentrated gels reduced in stiffness, whilst a biphasic pattern of increasing and then decreasing stiffness was observed at higher concentrations. Analysis of these cultures by PCR revealed a program of shifting integrin expression and highly variable activity in key morphogenic signal pathways, such as mitogen-associated protein kinase, indicating genetic impact of biomaterial interactions via mechano-regulation. Gel contraction at lower concentrations was also found to be accompanied by an increase in average collagen fibre diameter. Minor changes in biomaterial mechanics result in significant changes in programmed cell behaviour, resulting in adoption of markedly different cell morphologies and ability to remodel the scaffold. Advanced understanding of cell-biomaterial interactions, over short and long-term culture, is of critical importance in the development of novel tissue engineering strategies for the fabrication of biomimetic 3D neuro-tissue constructs. Simple methods of tailoring the initial mechanical environment presented to SH-SY5Y populations in 3D can lead to significantly different programs of network development over time. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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