The cytoplasm of living cells behaves as a poroelastic material

The mechanical properties of cells and tissues play a well-known role in physiology and disease. The model organism Caenorhabditis elegans exhibits mechanical properties that are still poorly understood, but are thought to be dominated by its collagen-rich outer cuticle. To our knowledge, we use a novel microfluidic technique to reveal that the worm responds linearly to low applied hydrostatic stress, exhibiting a volumetric compression with a bulk modulus, k ¼ 140 5 20 kPa; applying negative pressures leads to volumetric expansion of the worm, with a similar bulk modulus. Surprisingly, however, we find that a variety of collagen mutants and pharmacological perturbations targeting the cuticle do not impact the bulk modulus. Moreover, the worm exhibits dramatic stiffening at higher stresses-behavior that is also independent of the cuticle. The stress-strain curves for all conditions can be scaled onto a master equation, suggesting that C. elegans exhibits a universal elastic response dominated by the mechanics of pressurized internal organs.

Section: Using Hydrostatic Pressure To Probe C Elegans Mechanicssupporting

confidence: 81%

Section: Worms Expand Under Negative Applied Pressuresupporting

confidence: 76%

Worms under Pressure: Bulk Mechanical Properties of C. elegans Are Independent of the Cuticle

Gilpin

Uppaluri

Brangwynne

2015

“…Indeed, in another study, a millisecond-timescale platform measured higher cellular stiffness values than did AFM, which typically involves measurements on the timescale of seconds (59). In the future, it would be valuable to measure bead or cellular mechanical properties across various timescales within the same device.…”

Section: Discussionmentioning

confidence: 99%

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

Guillou

Dahl

Lin

et al. 2016

The quantification of cellular mechanical properties is of tremendous interest in biology and medicine. Recent microfluidic technologies that infer cellular mechanical properties based on analysis of cellular deformations during microchannel traversal have dramatically improved throughput over traditional single-cell rheological tools, yet the extraction of material parameters from these measurements remains quite complex due to challenges such as confinement by channel walls and the domination of complex inertial forces. Here, we describe a simple microfluidic platform that uses hydrodynamic forces at low Reynolds number and low confinement to elongate single cells near the stagnation point of a planar extensional flow. In tandem, we present, to our knowledge, a novel analytical framework that enables determination of cellular viscoelastic properties (stiffness and fluidity) from these measurements. We validated our system and analysis by measuring the stiffness of cross-linked dextran microparticles, which yielded reasonable agreement with previously reported values and our micropipette aspiration measurements. We then measured viscoelastic properties of 3T3 fibroblasts and glioblastoma tumor initiating cells. Our system captures the expected changes in elastic modulus induced in 3T3 fibroblasts and tumor initiating cells in response to agents that soften (cytochalasin D) or stiffen (paraformaldehyde) the cytoskeleton. The simplicity of the device coupled with our analytical model allows straightforward measurement of the viscoelastic properties of cells and soft, spherical objects.

“…Similarly, during invasion into tissues, tumor cells use actomyosin activity to squeeze through tight interstitial spaces (5). During these processes, the cell size, rheological properties and the geometric parameters associated with the extracellular environment dictate the maximal rate at which the cell can transmigrate and change its shape (6,7). The nucleus, being the largest and the stiffest organelle within the cell, is a physical constraint to migration and may be a rate-limiting factor for cellular deformations during cell migration through three-dimensional (3D) constrictions that are smaller or comparable to the nuclear cross section (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Cao

Moeendarbary

Isermann

et al. 2016

Self Cite

116

160

It is now evident that the cell nucleus undergoes dramatic shape changes during important cellular processes such as cell transmigration through extracellular matrix and endothelium. Recent experimental data suggest that during cell transmigration the deformability of the nucleus could be a limiting factor, and the morphological and structural alterations that the nucleus encounters can perturb genomic organization that in turn influences cellular behavior. Despite its importance, a biophysical model that connects the experimentally observed nuclear morphological changes to the underlying biophysical factors during transmigration through small constrictions is still lacking. Here, we developed a universal chemomechanical model that describes nuclear strains and shapes and predicts thresholds for the rupture of the nuclear envelope and for nuclear plastic deformation during transmigration through small constrictions. The model includes actin contraction and cytosolic back pressure that squeeze the nucleus through constrictions and overcome the mechanical resistance from deformation of the nucleus and the constrictions. The nucleus is treated as an elastic shell encompassing a poroelastic material representing the nuclear envelope and inner nucleoplasm, respectively. Tuning the chemomechanical parameters of different components such as cell contractility and nuclear and matrix stiffnesses, our model predicts the lower bounds of constriction size for successful transmigration. Furthermore, treating the chromatin as a plastic material, our model faithfully reproduced the experimentally observed irreversible nuclear deformations after transmigration in lamin-A/C-deficient cells, whereas the wild-type cells show much less plastic deformation. Along with making testable predictions, which are in accord with our experiments and existing literature, our work provides a realistic framework to assess the biophysical modulators of nuclear deformation during cell transmigration.