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1دورية أكاديمية
المؤلفون: Angela Mitevska, Citlally Santacruz, Eric J. Martin, Ian E. Jones, Arian Ghiacy, Simon Dixon, Nima Mostafazadeh, Zhangli Peng, Evangelos Kiskinis, John D. Finan
المصدر: Neurotrauma Reports, Vol 4, Iss 1, Pp 682-692 (2023)
مصطلحات موضوعية: finite element models, in vitro studies, models of injury, stem cells, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
الوصف: Human induced pluripotent stem cell (hiPSC)-derived cells can reproduce human-specific pathophysiology, patient-specific vulnerability, and gene-environment interactions in neurological disease. Human in vitro models of neurotrauma therefore have great potential to advance the field. However, this potential cannot be realized until important biomaterials challenges are addressed. Status quo stretch injury models of neurotrauma culture cells on sheets of polydimethylsiloxane (PDMS) that are incompatible with long-term monoculture of hiPSC-derived neurons. Here, we overcame this challenge in an established human in vitro neurotrauma model by replacing PDMS with a highly biocompatible form of polyurethane (PU). This substitution allowed long-term monoculture of hiPSC-derived neurons. It also changed the biomechanics of stretch injury. We quantified these changes experimentally using high-speed videography and digital image correlation. We used finite element modeling to quantify the influence of the culture substrate's thickness, stiffness, and coefficient of friction on membrane stretch and concluded that the coefficient of friction explained most of the observed biomechanical changes. Despite these changes, we demonstrated that the modified model produced a robust, dose-dependent trauma phenotype in hiPSC-derived neuron monocultures. In summary, the introduction of this PU film makes it possible to maintain hiPSC-derived neurons in monoculture for long periods in a human in vitro neurotrauma model. In doing so, it opens new horizons in the field of neurotrauma by enabling the unique experimental paradigms (e.g., isogenic models) associated with hiPSC-derived neurons.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2689-288X
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2دورية أكاديمية
المؤلفون: Sara Cardona, Nima Mostafazadeh, Qiyue Luan, Jian Zhou, Zhangli Peng, Ian Papautsky
المصدر: Micromachines, Vol 14, Iss 9, p 1665 (2023)
مصطلحات موضوعية: microfluidic cell trapping, hydrodynamic trapping, physical trapping, finite element method, cell isolation, Mechanical engineering and machinery, TJ1-1570
الوصف: Microfluidic methods have proven to be effective in separation and isolation of cells for a wide range of biomedical applications. Among these methods, physical trapping is a label-free isolation approach that relies on cell size as the selective phenotype to retain target cells on-chip for follow-up analysis and imaging. In silico models have been used to optimize the design of such hydrodynamic traps and to investigate cancer cell transmigration through narrow constrictions. While most studies focus on computational fluid dynamics (CFD) analysis of flow over cells and/or pillar traps, a quantitative analysis of mechanical interaction between cells and trapping units is missing. The existing literature centers on longitudinally extended geometries (e.g., micro-vessels) to understand the biological phenomenon rather than designing an effective cell trap. In this work, we aim to make an experimentally informed prediction of the critical pressure for a cell to pass through a trapping unit as a function of cell morphology and trapping unit geometry. Our findings show that a hyperelastic material model accurately captures the stress-related softening behavior observed in cancer cells passing through micro-constrictions. These findings are used to develop a model capable of predicting and extrapolating critical pressure values. The validity of the model is assessed with experimental data. Regression analysis is used to derive a mathematical framework for critical pressure. Coupled with CFD analysis, one can use this formulation to design efficient microfluidic devices for cell trapping and potentially perform downstream analysis of trapped cells.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Ik Sung Cho, Prerak Gupta, Nima Mostafazadeh, Sing Wan Wong, Saiumamaheswari Saichellappa, Stephen Lenzini, Zhangli Peng, Jae‐Won Shin
المصدر: Advanced Science, Vol 10, Iss 3, Pp n/a-n/a (2023)
مصطلحات موضوعية: cell polarity, microfluidics, hydrogels, microenvironments, cell encapsulation, Science
الوصف: Abstract Various signals in tissue microenvironments are often unevenly distributed around cells. Cellular responses to asymmetric cell‐matrix adhesion in a 3D space remain generally unclear and are to be studied at the single‐cell resolution. Here, the authors developed a droplet‐based microfluidic approach to manufacture a pure population of single cells in a microscale layer of compartmentalized 3D hydrogel matrices with a tunable spatial presentation of ligands at the subcellular level. Cells elongate with an asymmetric presentation of the integrin adhesion ligand Arg‐Gly‐Asp (RGD), while cells expand isotropically with a symmetric presentation of RGD. Membrane tension is higher on the side of single cells interacting with RGD than on the side without RGD. Finite element analysis shows that a non‐uniform isotropic cell volume expansion model is sufficient to recapitulate the experimental results. At a longer timescale, asymmetric ligand presentation commits mesenchymal stem cells to the osteogenic lineage. Cdc42 is an essential mediator of cell polarization and lineage specification in response to asymmetric cell‐matrix adhesion. This study highlights the utility of precisely controlling 3D ligand presentation around single cells to direct cell polarity for regenerative engineering and medicine.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2198-3844
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4
المؤلفون: Ik Sung Cho, Prerak Gupta, Nima Mostafazadeh, Sing Wan Wong, Saiumamaheswari Saichellappa, Stephen Lenzini, Zhangli Peng, Jae‐Won Shin
المصدر: Advanced science (Weinheim, Baden-Wurttemberg, Germany).
مصطلحات موضوعية: General Chemical Engineering, General Engineering, General Physics and Astronomy, Medicine (miscellaneous), General Materials Science, Biochemistry, Genetics and Molecular Biology (miscellaneous)
الوصف: Various signals in tissue microenvironments are often unevenly distributed around cells. Cellular responses to asymmetric cell-matrix adhesion in a 3D space remain generally unclear and are to be studied at the single-cell resolution. Here, the authors developed a droplet-based microfluidic approach to manufacture a pure population of single cells in a microscale layer of compartmentalized 3D hydrogel matrices with a tunable spatial presentation of ligands at the subcellular level. Cells elongate with an asymmetric presentation of the integrin adhesion ligand Arg-Gly-Asp (RGD), while cells expand isotropically with a symmetric presentation of RGD. Membrane tension is higher on the side of single cells interacting with RGD than on the side without RGD. Finite element analysis shows that a non-uniform isotropic cell volume expansion model is sufficient to recapitulate the experimental results. At a longer timescale, asymmetric ligand presentation commits mesenchymal stem cells to the osteogenic lineage. Cdc42 is an essential mediator of cell polarization and lineage specification in response to asymmetric cell-matrix adhesion. This study highlights the utility of precisely controlling 3D ligand presentation around single cells to direct cell polarity for regenerative engineering and medicine.
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