Effect of Geometric Curvature on Collective Cell Migration in Tortuous Microchannel Devices

Abstract

<jats:p>Collective cell migration is an essential phenomenon in many naturally occurring pathophysiological processes, as well as in tissue engineering applications. Cells in tissues and organs are known to sense chemical and mechanical signals from the microenvironment and collectively respond to these signals. For the last few decades, the effects of chemical signals such as growth factors and therapeutic agents on collective cell behaviors in the context of tissue engineering have been extensively studied, whereas those of the mechanical cues have only recently been investigated. The mechanical signals can be presented to the constituent cells in different forms, including topography, substrate stiffness, and geometrical constraint. With the recent advancement in microfabrication technology, researchers have gained the ability to manipulate the geometrical constraints by creating 3D structures to mimic the tissue microenvironment. In this study, we simulate the pore curvature as presented to the cells within 3D-engineered tissue-scaffolds by developing a device that features tortuous microchannels with geometric variations. We show that both cells at the front and rear respond to the varying radii of curvature and channel amplitude by altering the collective migratory behavior, including cell velocity, morphology, and turning angle. These findings provide insights into adaptive migration modes of collective cells to better understand the underlying mechanism of cell migration for optimization of the engineered tissue-scaffold design.</jats:p>

Review on Porous Scaffolds Generation Process: A Tissue Engineering Approach

“…10 These concepts are starting to gain attention since they explain certain phenomena that can affect the complete scaffold, like a failure in cell attachment due to high curved struts 11 or due to high shear stress at the wall of pore size, 12 different rates of migration in curved surfaces, 13 and differentiation due to mechanical cues. 14 Due to the difficulty in controlling the pore at a cellular scale with current fabrication methods, mechanobiology has been studied mostly with computer-in silico models 15 or evaluated in single blocks and curved substrates, 16,17 using wavy landscapes, 18 microcurved channels, 19 or semispherical wells with different radii of curvature. 13,20 There are 524 articles on lens.org that relate scaffolds and mechanobiology in the past five years, and only 138 also include the term porous.…”

Tissue flow through pores: a computational study

“…The focus of our work lies on the internal structure and single-cell dynamics inside the sheet and how it is influenced by a bottleneck. Previous works, both experimental [9, 10, 11, 12, 17, 13, 14, 16] and numerical [25, 42], have concentrated on velocity and density fields or the shape of the invasion front in channels of constant [9, 10, 11, 12, 17, 13, 14, 16, 25, 42] or linearly changing [17, 25] diameter. In many of these studies strong density fluctuations in the channel are reported, a feature that our model did not reproduce.…”

“…To investigate how such extracellular constraints alter cellular behaviour, idealised in-vitro experiments have been set up in environments with different geometries [6]. This has been realised for single cells that squeeze through tight capillaries [7, 8], but also in numerous experiments on collective cellular assemblies in diverse settings like straight 2D troughs [9, 10, 11, 12, 13, 14] and 3D tubes [15], winding canals [16], and expanding or narrowing channels [17]. The general question is what phenomenological effects are induced by external confinement and guidance, for example regarding flow behaviour, cell shape, spatial arrangement of cells in the cell sheet, or cell division.…”

Current Development in Interdigital Transducer (IDT) Surface Acoustic Wave Devices for Live Cell In Vitro Studies: A Review

“…Cell migration is crucial in physiological and pathological processes, such as wound healing, angiogenesis, morphogenesis, and cancer metastasis [50,51]. Although the majority of studies use chemical variables, it was reported that mechanical stimulation can dramatically control cell migration by electrical cue [52,53], substrate stiffness [54,55], stretching [56], and acoustic waves [57]. Most of these simulations are based on invasive procedures, except electrical and acoustic waves cues [58,59].…”