Onal Sevgi, Alkaisi Maan M, Nock Volker
Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand.
MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand.
Heliyon. 2024 Dec 30;11(1):e41433. doi: 10.1016/j.heliyon.2024.e41433. eCollection 2025 Jan 15.
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.
尽管随机基因突变的积累传统上被视为癌症进展的主要原因，但细胞和微环境中机械生物学特征的改变作为一种与突变无关的因素也起着重要作用。为了探究后者，我们之前报道了一种集成了柔性致动器的微流控细胞培养平台及其在癌细胞顺序循环压缩中的应用。该平台由顶层的控制微通道组成，用于引入外部压力，以及一个聚二甲基硅氧烷（PDMS）膜，一个整体集成的致动器从该膜向下突出到细胞培养微通道中。当被驱动时，这个被称为微活塞的集成致动器将来自控制通道的压力作为机械力传递给下面的细胞。当不被驱动时，微活塞悬浮在细胞上方，通过约108μm的充满液体的间隙与细胞隔开。尽管在后面这种排列中微活塞与细胞之间缺乏直接的物理接触，但我们观察到SKOV - 3卵巢癌细胞明显与活塞形状对齐。为了表征这一观察结果，我们调整了微活塞的定位、形状和大小，并探究了单层SKOV - 3细胞相对于悬浮结构的方向性。通过测量整个细胞体相对于微活塞周边的伸长角度，以一种新颖的无标记方法进行细胞对齐分析。与同一芯片上没有微活塞的对照区域相比，SKOV - 3细胞与圆形、三角形和方形微活塞的结构轮廓对齐是显著的。无论细胞是在静态位置（约108μm间隙）加载微活塞，还是使用真空主动缩回（>108μm间隙），这种效果都存在。在MCF7癌细胞和MCF10A非癌性上皮细胞中未观察到类似的对齐现象。所报道的SKOV - 3细胞向微活塞下方区域的定向运动和生长的观察结果表明，这些细胞存在一种迄今为止尚未被探索的趋机械性的行为，这需要对其中涉及的机制以及它们在癌症中可能发挥的作用进行进一步研究。
