3rd International Congress on Biomedicine (ICB2019)
Organ-On-Chip Disease Models to Investigate Cell Deformability: Review
Organ-On-Chip Disease Models to Investigate Cell Deformability: Review
Hamide Ehtesabi,1,*
1. Faculty of Life Sciences and Biotechnology, ShahidBeheshti University G.C., Tehran, Iran
Introduction: Conventional Models for Therapeutic development
Therapeutic development often relies heavily upon model systems. This enables high‐throughput analysis of the role of growth factors, cytokines, and pharmaceutical agents (Biglari et al. 2019). Many models in which various aspects of a disease can be reproduced were designed and rigorously tested. These models range from small and large animals, cell and tissue cultures, and the recent advent of tissue-engineered organoids (Hwang and Lu 2013). These approaches have advantages and limitations, specifically depending upon the purpose of the application. Developmental biology has advanced the understanding of the intricate and dynamic processes involved in the formation of an organism from a single cell (Samal et al. 2019).
Methods: An organ‐on‐chip consists of a microfluidic device composed of a variety of cell types cultured in different layers that can interact with each other, in a highly controlled microenvironment, while mimicking the complex cell-cell and cell-matrix interactions. (Biglari et al. 2019). Organ-on-chip is broadly defined by the minimum amount of assembly of cells in a microenvironment that leads to mimicry of an organ-level function of a human (Gold, Gaharwar, and Jain 2019). The goal of an Organ-on-chip is not to build a whole living organ but rather to establish a minimally functional unit that can recapitulate certain aspects of human physiology in a controlled and straightforward manner (Ronaldson-Bouchard and Vunjak-Novakovic 2018). Organ-on-chip is a good candidate for disease models. A disease model is cells displaying all or some of the pathological processes that are observed in the actual human disease. Studying disease models aids understanding of how the disease develops and testing potential treatment approaches. In this study organ-on-chip disease models to investigate cell deformability reviewed.
Results: The association between cell deformability and human diseases has been of interest since the 1960s. The deformability of nucleated cells is determined by the membrane, the cytoskeletal network (actin filaments, intermediate filaments, and microtubules), and its interaction with the nucleus, while the deformability of red blood cells (RBCs) is determined by the membrane skeleton network and the interaction between the membrane skeleton and membrane integral proteins. Physiological and pathological changes can alter the cytoskeleton composition, reorganize the network structure, and change the protein density. As a result, cell deformability can be used as an intrinsic marker for identifying pathological conditions.
Conclusion: Zheng et al. show that deformability is known to play a crucial role in the mobility of cancerous cells; and a decrease in RBC deformability has been proven to be relevant in several human diseases (Zheng et al. 2013). In another research, cell deformability used in both shear-dominant and inertia-dominant microfluidic flow regimes to probe different aspects of the cell structure. In the inertial regime, cellular response from (visco-)elastic followed through plastic deformation to cell structural failure and showed a significant drop in cell viability for shear stresses >11.8 kN/m2. Comparatively, a shear-dominant regime requires lower applied stresses to achieve higher cell strains. These results emphasize the benefit of multiple parameter determination for improving detection and will ultimately lead to improved accuracy for diagnosis. The shear regime is more sensitive to cytoskeletal changes, and that large strains in the inertial regime cannot resolve changes to the actin cytoskeleton. Deformation of HL60 cells as a function of flow rate in the inertia-dominant and shear-dominant regimes show cell response is dependent upon the nature of the applied force (shear, compressive) and not simply the amplitude of the force. Cells appear stiffer in an inertial regime (low viscosity, high flow rate) compared to a shear regime (high viscosity, low flow rate). This behavior indicates that different deformation regimes are likely to be sensitive to different subcellular components. The microfluidic approach offers a high-throughput technique for the cell mechanophenotyping as well as increases the range of deformability (1.3 < DI < 2.8) and strain rates (103105 Hz) that can be achieved. Armisted et al. performed Microfluidic deformation assays to phenotype two different cell lines. HL60 is a circulating leukemia cell line expected to exhibit a more deformable response compared to SW480 cells, which originate from a solid colorectal cancer tumor. SW480 cells were also treated with an actin-cytoskeleton-disrupting drug, latrunculin A (LatA; Cayman Chemical, Ann Arbor, MI), to determine the sensitivity of the different flow regimes to changes in the actin cytoskeleton. By studying both regimes, They show that specific flow conditions probe different aspects of the cell structure, demonstrating that a shear-dominant and low-strain regime is most sensitive to cytoskeletal changes. These results show the potential of relaxation time as a biophysical marker for mechanical phenotyping and that multiparameter analysis is vital for furthering understanding of cell mechanics (Armistead et al. 2019)