Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(3), P. 281 - 297

Published: Jan. 29, 2024

Language: Английский

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Single-Cell Mechanics: Structural Determinants and Functional Relevance

Annual Review of Biophysics, Journal Year: 2024, Volume and Issue: 53(1), P. 367 - 395

Published: Feb. 21, 2024

The mechanical phenotype of a cell determines its ability to deform under force and is therefore relevant cellular functions that require changes in shape, such as migration or circulation through the microvasculature. On practical level, can be used global readout cell's functional state, marker for disease diagnostics, an input tissue modeling. We focus our review on current knowledge structural components contribute determination properties highlight physiological processes which cells critical relevance. ongoing efforts understand how efficiently measure control will define progress field drive phenotyping toward clinical applications.

Language: Английский

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Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Sept. 2, 2022

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular health disease. We present a high-throughput, simple low-cost microfluidic method for quantitatively the elastic (storage) viscous (loss) modulus of individual cells. Cells suspended high-viscosity fluid pumped with high pressure through 5.8 cm long 200 µm wide channel. The shear stress induces large, ear ellipsoidal deformations. In addition, flow profile channel causes cells to rotate tank-treading manner. From deformation tank treading frequency, we extract frequency-dependent properties based on theoretical framework developed R. Roscoe [1] that describes sphere under steady laminar flow. confirm accuracy using atomic force microscopy-calibrated polyacrylamide beads Our measurements demonstrate exhibit power-law, soft glassy rheological behavior is cell-cycle-dependent mediated physical interplay between actin filament intermediate networks.Cells human body viscoelastic: they have some an solid, like rubber, as well fluid, oil. To carry out mechanical tasks – such as, migrating tissues heal wound or fight inflammation need right balance viscosity elasticity. Measuring these two therefore researchers understand important how impacted However, quantifying tricky, both depend time-scale measured: when pressed slowly, appear liquid, but turn hard thick rapidly pressed. Here, Gerum et al. new system elasticity fast, simple, inexpensive. this method, specialized solution consistency similar machine oil which then pushed channels less than half millimeter wide. resulting shears cells, causing elongate rotate, captured fast camera takes 500 images per second. used artificial intelligence each cell’s shape rotation speed from images, calculated their existing theories objects behave fluids. also investigated changed frequencies, corresponds shorter time-scales. This revealed while frequencies made more elastic, ratio remained same. means compare results obtained different experimental techniques, even if were carried at completely provides inexpensive way analyzing It could be useful tool screening effects drugs, diagnostic detect diseases affect

Language: Английский

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Calcium supplementation of bioinks reduces shear stress-induced cell damage during bioprinting

Biofabrication, Journal Year: 2022, Volume and Issue: 14(4), P. 045005 - 045005

Published: July 27, 2022

Abstract During bioprinting, cells are suspended in a viscous bioink and extruded under pressure through small diameter printing needles. The combination of high needle exposes to considerable shear stress, which can lead cell damage death. Approaches monitor control stress-induced currently not well established. To visualize the effects printing-induced stress on plasma membrane integrity, we add FM 1-43 bioink, styryl dye that becomes fluorescent when bound lipid membranes, such as cellular membrane. Upon disruption, enters also stains intracellular membranes. Extrusion alginate-suspended NIH/3T3 200 µ m led an increased incorporation at pressure, demonstrating typical stresses during bioprinting transiently Cell imaging microfluidic channel confirmed is caused by strain. Notably, impaired survival experiments. Using types different stiffnesses, find strain, death were reduced stiffer compared softer demonstrate correlate with deformation. Importantly, supplementation suspension medium physiological concentrations CaCl 2 greatly but As sudden influx calcium ions known induce rapid vesicle exocytosis subsequent actin polymerization cortex, hypothesize facilitates resealing sites. We recommend bioinks should be routinely supplemented reduce extrusion bioprinting.

Language: Английский

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Size- and position-dependent cytoplasm viscoelasticity through hydrodynamic interactions with the cell surface

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(9)

Published: Feb. 21, 2023

Many studies of cytoplasm rheology have focused on small components in the submicrometer scale. However, also baths large organelles like nuclei, microtubule asters, or spindles that often take significant portions cells and move across to regulate cell division polarization. Here, we translated passive sizes ranging from few up ~50 percents diameter, through vast live sea urchin eggs, with calibrated magnetic forces. Creep relaxation responses indicate for objects larger than micron size, behaves as a Jeffreys material, viscoelastic at short timescales, fluidizing longer times. component size approached cells, resistance increased nonmonotonic manner. Flow analysis simulations suggest this size-dependent viscoelasticity emerges hydrodynamic interactions between moving object static surface. This effect yields position-dependent initially closer surface being harder displace. These findings hydrodynamically couples restrain their motion, important implications shape sensing cellular organization.

Language: Английский

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High-throughput viscoelastic characterization of cells in hyperbolic microchannels

Lab on a Chip, Journal Year: 2024, Volume and Issue: 24(9), P. 2440 - 2453

Published: Jan. 1, 2024

We use hyperbolic microchannels to create a flow field with linearly increasing velocity, leading constant tensile stress probe the viscoelastic properties of cells. verify our approach on oil droplets and polyacrylamide beads.

Language: Английский

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Advances in mechanical biomarkers

Journal of Molecular Recognition, Journal Year: 2023, Volume and Issue: 36(8)

Published: April 24, 2023

Abstract Mechanical biomarkers distinguish health conditions through quantitative mechanical measurements. The emergence and establishment of nanotechnology in the last decades have provided new tools to obtain at nanoscale. measurements are reproducible, label‐free, start be applied vivo can high throughput, require small samples. protocols clinical practice macro scale like palpation or blood pressure measurement routinely used by medical doctors. Nanotechnology brought sensing next scale, where cells, tissues, proteins probed linked conditions. changes cells tissues may detected before other markers, such as protein expression, providing an important advantage biomarkers. In present review, we explore biomarker's historical evolution, describe on various diseases novel discoveries nanomechanical field for their characterization. We conclude that establishing hallmarks diseases, several cases early diagnostics discovery drug targets involved changes, while advances instrumentation bringing commercial products into practice. along with testing niche market, whose demand is increasing due expansion personalized medicine unmet needs clinics.

Language: Английский

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Single-cell mechanical characterization in constriction-based cytometry

International Journal of Mechanical Sciences, Journal Year: 2024, Volume and Issue: 268, P. 108979 - 108979

Published: Jan. 5, 2024

Mechanical characterization of suspended cells by constriction-based microfluidic devices has currently various limitations related to the available analysis models. In this work, we propose a new methodology analyze experiments. This approach is based on numerical simulations describe fluid forces and cell deformation an extension quasi-linear viscoelasticity theory developed Fung. The are considered visco-hyperelastic, homogeneous, isotropic. allows for assessing mechanical parameters individual cells, which not possible using previous approaches, notably increasing power technique. A practical procedure compute proposed demonstrated analyzing experiments with cells. in work provides convenient tool overcome critical state art leverage potential these devices.

Language: Английский

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Advantages of integrating Brillouin microscopy in multimodal mechanical mapping of cells and tissues

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102341 - 102341

Published: March 11, 2024

Language: Английский

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Single-cell mechanical assay unveils viscoelastic similarities in normal and neoplastic brain cells

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(9), P. 1098 - 1105

Published: March 27, 2024

Understanding cancer cell mechanics allows for the identification of novel disease mechanisms, diagnostic biomarkers, and targeted therapies. In this study, we utilized our previously established fluid shear stress assay to investigate compare viscoelastic properties normal immortalized human astrocytes invasive glioblastoma (GBM) cells when subjected physiological levels that are present in brain microenvironment. We used a parallel-flow microfluidic system camera-coupled optical microscope expose single monitor resulting deformation real time, respectively. From video-rate imaging, fed information from digital image correlation into three-parameter generalized Maxwell model quantify nuclear cytoplasmic cells. further quantified actin cytoskeleton density alignment GBM via fluorescence microscopy analysis techniques. Results study show contrary behavior many extracranial cells, cancerous do not exhibit significant differences their properties. Moreover, also found nucleus cytoplasm as well cytoskeletal densities both types similar. Our work suggests malignant unique mechanical behaviors seen other types. These results warrant future studies elucidate distinct biophysical characteristics reveal attributes primary tumors.

Language: Английский

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