Published on 23 August 2021
The demonstrated system employs a fine and extensive control of the pressure amount, duration, and profile to apply dynamic cell compression, at a whole range of physiological pressure levels, as well as milder and severe pressures. This dynamic compression capability of the platform enables investigation of the cell response from mechanical stimulation to deformation to lysis. This work originates from an article entitled “A Flexible Microdevice for Mechanical Cell Stimulation and Compression in Microfluidic Settings” written by Sevgi Onal, Maan M. Alkaisi, Volker Nock and published in the journal “Frontiers in Physics”, where the authors show the design, fabrication and application of microfluidics-based flexible microdevices to apply mechanical stimulation and compression on living cells.
Compressive stress by tumor growth and stromal tissue alters cell deformation and recapitulates the biophysical properties of cells to grow, differentiate, spread, invade, or lyse. This work offers a microfluidic cell culture platform composed of a control microchannel in a top layer for introducing external force and a flexible membrane with monolithically integrated actuators to apply compression on cancer cells in a dynamic and controlled manner by modulating applied gas pressure, localization, shape, and size of the actuator. The ability for active modulation of the applied pressure in repeated (i.e., cyclic) and sequential manner allows the application of dynamic cell compression at physiological pressure levels and end point mechanical cell lysis in a single device, demonstrating the suitability of the platform to study the role of compressive forces in cancer microenvironments.
Biomechanical forces regulate tumor microenvironment by solid stress, matrix mechanics, interstitial pressure, and flow [1]. Compressive stress alters the cell deformation, and recapitulates the biophysical properties of cells to grow, differentiate, spread, invade, or lyse [2]. Such a solid stress can be introduced externally to change the cell response and to mechanically induce cell stimulation and lysis by dynamic compression. The concept of applying mechanical compression on living cells such as cancer cells, stromal cells, neurons, and chondrocytes gained importance at recent years. While mechanical compression on living cells has been applicable in bulk systems, controlled and dynamic compression can be achieved particularly in microfluidic settings. Microfluidic systems can be designed to have integrated physical structures introducing static and dynamic physical inputs, as well as gradients, and enabling real-time imaging. As demonstrated in this work, microfluidics-based in vitro culture systems can mimic in vivo physical microenvironments where compressive force application can be controlled spatially and temporally, providing a useful tool to study biomechanics of the living cells [3-5].
Fig 1. Concept of compression application in a flexible microdevice and evolution of cell viability response as per increasing gas pressures applied via a pressure-driven flow controller. Available here from Onal et al (2021) research article.
• To apply mechanical cell compression dynamically via microfluidics. • To fine-tune the dynamic compression process while exposing the cells to a variety of pressures to regulate the cell response from mechanical stimulation, to deformation, and to lysis. • To experimentally mimic the physiological compression process in cyclic manner and obtain good position recovery of the compressing unit between the cycles.
Fig. 2 Pressure-driven flow control setup for applying and sensing external pressure through the control microchannel in a cell compression microdevice. Available here from Onal et al (2021) research article.
This work introduces a flexible multilayer microdevice with a micro-piston suspended into the cell culture chamber for dynamic mechanical cell stimulation and compression to investigate the cell response to varying pressures applied in ascending order (Fig. 1 and Video 1).
Characterization of the micro-piston actuation was done using optical imaging methods and two different external pressure system types, adding flexibility based on the laboratory requirements, with extensive use of Elveflow’s OB1 pressure-driven flow controller, microfluidic pressure sensors and sensor reader (Fig. 2 and Fig. 3).
Fig. 3 Graphs of applied and measured pressure profiles in a flexible microdevice. Courtesy of Sevgi Onal.
The ability of the platform to apply cyclic and varying compression profiles sequentially was tested, demonstrating that it can be used to mimic the chronic mechanical stimuli the cells are exposed to in ovarian cancer metastasis (Fig. 3 and Video 1).
Temporal evolution of the dynamic pressure control on cell compression and deformation with different pressure amounts, time length and cyclic mode is shown in Video 2.
The applicability of the cyclic compression with this platform was further illustrated by capturing the actin and nuclear deformation in the cyclically compressed cells (Fig. 4).
These results demonstrate suitability of the flexible microdevice for mechanical stimulation with various physiological pressures based on live-and-dead cell assay and mechanobiologically related protein profile to study cell biomechanics and compressive forces in cancer microenvironments.
Furthermore, usage of the platform has recently been extended by Onal et al. (2021) to the application of sequential cyclic compression to study the dynamics of live cell actin and to investigate the recovery of the compressed cells [5].
Fig. 4 Pictures of control and cyclically compressed cells and their actin and nuclei profiles. Courtesy of Sevgi Onal.
Courtesy of Sevgi Onal and Volker Nock – Cyclic compression of a SKOV-3 cancer cell monolayer at mild and then higher pressures obtained with OB1 Mk2 Elveflow pressure-driven flow controller coupled with MPS and MSR.
Courtesy of Sevgi Onal and Volker Nock – Temporal evolution of the pressure control in dynamic cell compression obtained with OB1 Mk2 Elveflow pressure-driven flow controller coupled with MPS and MSR.
If you are interested in reproducing what Sevgi Onal achieved in her work, feel free to contact our team of experts for additional information about the OB1 pressure-driven flow controller for fine tuning of your fluid flow!
You can also read this related content on cell confinement and mechanical stress of cells and tissues using microfluidics.
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