On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures

Although the accumulation of random genetic mutations has been traditionally viewed as the main cause of cancer progression, altered mechanobiological profiles of the cells and microenvironment also play a major role as a mutation-independent element. To probe the latter, we have previously reported...

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Main Authors: Sevgi Onal, Maan M. Alkaisi, Volker Nock
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024174646
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author Sevgi Onal
Maan M. Alkaisi
Volker Nock
author_facet Sevgi Onal
Maan M. Alkaisi
Volker Nock
author_sort Sevgi Onal
collection DOAJ
description Although the accumulation of random genetic mutations has been traditionally viewed as the main cause of cancer progression, altered mechanobiological profiles of the cells and microenvironment also play a major role as a mutation-independent element. To probe the latter, we have previously reported a microfluidic cell-culture platform with an integrated flexible actuator and its application for sequential cyclic compression of cancer cells. The platform is composed of a control microchannel in a top layer for introducing external pressure, and a polydimethylsiloxane (PDMS) membrane from which a monolithically-integrated actuator protrudes downwards into a cell-culture microchannel. When actuated, the integrated actuator, referred to as micro-piston, transfers the pressure from the control channel as a mechanical force to the cells underneath. When not actuated, the micro-piston remains suspended above cells, separated from the latter via a liquid-filled gap of ∼108 μm. Despite the lack of direct physical contact between the micro-piston and cells in the latter arrangement, we observed distinct alignment of SKOV-3 ovarian cancer cells to the piston shape. To characterize this observation, micro-piston localization, shape, and size were adjusted and the directionality of a mono-layer of SKOV-3 cells relative to the suspended structure was probed. Cell alignment analysis was performed in a novel, label-free approach by measuring elongation angles of whole cell bodies with respect to micro-piston peripheries. Alignment of SKOV-3 cells to the structure outline was significant for circular, triangular and square micro-piston when compared to control areas without micro-piston on the same chip. The effect was present irrespective of whether cells were loaded with micro-pistons in static position (∼108 μm gap) or actively retracted using vacuum (>108 μm gap). Similar alignment was not observed for MCF7 cancer cells and MCF10A non-cancerous epithelial cells. The reported observation of directional movement and growth of SKOV-3 cells towards the region under micro-pistons point towards a to-date unexplored mechanotactic behavior of these cells, warranting future investigations regarding the mechanisms involved and the role these may play in cancer.
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spelling doaj-art-7c7352a9d44949518ee19a930aa1a0c42025-01-17T04:51:15ZengElsevierHeliyon2405-84402025-01-01111e41433On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructuresSevgi Onal0Maan M. Alkaisi1Volker Nock2Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand; Corresponding authors at: Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand.Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New ZealandElectrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand; MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand; Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand; Corresponding authors at: Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand.Although the accumulation of random genetic mutations has been traditionally viewed as the main cause of cancer progression, altered mechanobiological profiles of the cells and microenvironment also play a major role as a mutation-independent element. To probe the latter, we have previously reported a microfluidic cell-culture platform with an integrated flexible actuator and its application for sequential cyclic compression of cancer cells. The platform is composed of a control microchannel in a top layer for introducing external pressure, and a polydimethylsiloxane (PDMS) membrane from which a monolithically-integrated actuator protrudes downwards into a cell-culture microchannel. When actuated, the integrated actuator, referred to as micro-piston, transfers the pressure from the control channel as a mechanical force to the cells underneath. When not actuated, the micro-piston remains suspended above cells, separated from the latter via a liquid-filled gap of ∼108 μm. Despite the lack of direct physical contact between the micro-piston and cells in the latter arrangement, we observed distinct alignment of SKOV-3 ovarian cancer cells to the piston shape. To characterize this observation, micro-piston localization, shape, and size were adjusted and the directionality of a mono-layer of SKOV-3 cells relative to the suspended structure was probed. Cell alignment analysis was performed in a novel, label-free approach by measuring elongation angles of whole cell bodies with respect to micro-piston peripheries. Alignment of SKOV-3 cells to the structure outline was significant for circular, triangular and square micro-piston when compared to control areas without micro-piston on the same chip. The effect was present irrespective of whether cells were loaded with micro-pistons in static position (∼108 μm gap) or actively retracted using vacuum (>108 μm gap). Similar alignment was not observed for MCF7 cancer cells and MCF10A non-cancerous epithelial cells. The reported observation of directional movement and growth of SKOV-3 cells towards the region under micro-pistons point towards a to-date unexplored mechanotactic behavior of these cells, warranting future investigations regarding the mechanisms involved and the role these may play in cancer.http://www.sciencedirect.com/science/article/pii/S2405844024174646MicrofluidicsMicro-pistonIn-channel hanging structuresCell alignmentCancer biomechanicsOvarian cancer
spellingShingle Sevgi Onal
Maan M. Alkaisi
Volker Nock
On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
Heliyon
Microfluidics
Micro-piston
In-channel hanging structures
Cell alignment
Cancer biomechanics
Ovarian cancer
title On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
title_full On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
title_fullStr On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
title_full_unstemmed On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
title_short On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
title_sort on chip non contact mechanical cell stimulation quantification of skov 3 alignment to suspended microstructures
topic Microfluidics
Micro-piston
In-channel hanging structures
Cell alignment
Cancer biomechanics
Ovarian cancer
url http://www.sciencedirect.com/science/article/pii/S2405844024174646
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