Poroelastic osmoregulation of living cell volume

Cells maintain their volume through fine intracellular osmolarity regulation. Osmotic challenges drive fluid into or out of cells causing swelling or shrinkage, respectively. The dynamics of cell volume changes depending on the rheology of the cellular constituents and on how fast the fluid permeates through the membrane and cytoplasm. We investigated whether and how poroelasticity can describe volume dynamics in response to osmotic shocks. We exposed cells to osmotic perturbations and used defocusing epifluorescence microscopy on membrane-attached fluorescent nanospheres to track volume dynamics with high spatiotemporal resolution. We found that a poroelastic model that considers both geometrical and pressurization rates captures fluid-cytoskeleton interactions, which are rate-limiting factors in controlling volume changes at short timescales. Linking cellular responses to osmotic shocks and cell mechanics through poroelasticity can predict the cell state in health, disease, or in response to novel therapeutics

Poroelastic osmoregulation of living cell volume

Cells maintain their volume through fine intracellular osmolarity regulation. Osmotic challenges drive fluid into or out of cells causing swelling or shrinkage, respectively. The dynamics of cell volume changes depending on the rheology of the cellular constituents and on how fast the fluid permeates through the membrane and cytoplasm. We investigated whether and how poroelasticity can describe volume dynamics in response to osmotic shocks. We exposed cells to osmotic perturbations and used defocusing epifluorescence microscopy on membrane-attached fluorescent nanospheres to track volume dynamics with high spatiotemporal resolution. We found that a poroelastic model that considers both geometrical and pressurization rates captures fluid-cytoskeleton interactions, which are rate-limiting factors in controlling volume changes at short timescales. Linking cellular responses to osmotic shocks and cell mechanics through poroelasticity can predict the cell state in health, disease, or in response to novel therapeutics.Peer ReviewedPostprint (published version

An IB Method for Non-Newtonian-Fluid Flexible-Structure Interactions in Three-Dimensions

Problems involving fluid flexible-structure interactions (FFSI) are ubiquitous in engineering and sciences. Peskin’s immersed boundary (IB) method is the first framework for modeling and simulation of such problems. This paper addresses a three-dimensional extension of the IB framework for non-Newtonian fluids which include power-law fluid, Oldroyd-B fluid, and FENE-P fluid. The motion of the non-Newtonian fluids are modelled by the lattice Boltzmann equations (D3Q19 model). The differential constitutive equations of Oldroyd-B and FENE-P fluids are solved by the D3Q7 model. Numerical results indicate that the new method is first-order accurate and conditionally stable. To show the capability of the new method, it is tested on three FFSI toy problems: a power-law fluid past a flexible sheet fixed at its midline, a flexible sheet being flapped periodically at its midline in an Oldroyd-B fluid, and a flexible sheet being rotated at one edge in a FENE-P fluid

Reciprocal theorem for linear poro-viscoelastic materials

In studying the transport of particles and inclusions in multi-phase systems we are often interested in integrated quantities such as the total force and the net velocity of the particles. Here, we derive a reciprocal formulation for linear poro-viscoelastic (PVE) materials, which are composed of a linear compressible viscoelastic phase, i.e. the network phase, permeated by a viscous fluid. As an application of the reciprocal theorem, we analytically calculate the time-dependent net force on a rigid stationary sphere in response to point-forces applied to the elastic network and Newtonian fluid phases of a PVE material. We show that the net force on the sphere in response to a point-force in the fluid phase evolves over timescales that are independent of the distance of the point-force to the sphere; in comparison, when the point-force is applied to the network phase the timescale for force development becomes distance-dependent. We discuss how in both cases these relaxation times are related to the physical timescales that are determined by mechanical properties of both phases -- such as the network's Poisson ratio, permeability and shear modules, and the fluid viscosity -- as well as geometric factors, including the size of the spherical inclusion and its distance from point-forces. The reciprocal theorem presented here can be applied to a wide range of problems involving the transport of cells, organelles and condensates in biological systems composed of filamentous networks permeated by viscous fluids

Modelling and simulations of hydrogels with coupled solvent diffusion and large deformation

textSwelling of a polymer gel is a kinetic process coupling mass transport and mechanical deformation. A comparison between a nonlinear theory for polymer gels and the classical theory of linear poroelasticity is presented. It is shown that the two theories are consistent within the linear regime under the condition of a small perturbation from an isotropically swollen state of the gel. The relationships between the material properties in the linear theory and those in the nonlinear theory are established by a linearization procedure. Both linear and nonlinear solutions are presented for swelling kinetics of substrate-constrained and freestanding hydrogel layers. A new procedure is suggested to fit the experimental data with the nonlinear theory. A nonlinear, transient finite element formulation is presented for initial boundary value problems associated with swelling and deformation of hydrogels, based on nonlinear continuum theories for hydrogels with compressible and incompressible constituents. The incompressible instantaneous response of the aggregate imposes a constraint to the finite element discretization in order to satisfy the LBB condition for numerical stability of the mixed method. Three problems of practical interests are considered: constrained swelling, flat-punch indentation, and fracture of hydrogels. Constrained swelling may lead to instantaneous surface instability. Indentation relaxation of hydrogels is simulated beyond the linear regime under plane strain conditions, and is compared with two elastic limits for the instantaneous and equilibrium states. The effects of Poisson’s ratio and loading rate are discussed. On the study of hydrogel fracture, a method for calculating the transient energy release rate for crack growth in hydrogels, based on a modified path-independent J-integral, is presented. The transient energy release rate takes into account the energy dissipation due to diffusion. Numerical simulations are performed for a stationary center crack loaded in mode I, with both immersed and non-immersed chemical boundary conditions. Both sharp crack and blunted notch crack models are analyzed over a wide range of applied remote tensile strains. Comparisons to linear elastic fracture mechanics are presented. A critical condition is proposed for crack growth in hydrogels based on the transient energy release rate. The applicability of this growth condition for simulating concomitant crack propagation and solvent diffusion in hydrogels is discussed.Engineering Mechanic

Theoretically proposed optimal frequency for ultrasound induced cartilage restoration

Background: Matching the frequency of the driving force to that of the system’s natural frequency of vibration results in greater amplitude response. Thus we hypothesize that applying ultrasound at the chondrocyte’s resonant frequency will result in greater deformation than applying similar ultrasound power at a frequency outside of the resonant bandwidth. Based on this resonant hypothesis, our group previously confirmed theoretically and experimentally that ultrasound stimulation of suspended chondrocytes at resonance (5 MHz) maximized gene expression of load inducible genes. However, this study was based on suspended chondrocytes. The resonant frequency of a chondrocyte does not only depend on the cell mass and intracellular stiffness, but also on the mechanical properties of the surrounding medium. An in vivo chondrocyte’s environment differs whether it be a blood clot (following microfracture), a hydrogel or the pericellular and extracellular matrices of the natural cartilage. All have distinct structures and compositions leading to different resonant frequencies. In this study, we present two theoretical models, the first model to understand the effects of the resonant frequency on the cellular deformation and the second to identify the optimal frequency range for clinical applications of ultrasound to enhance cartilage restoration. Results: We showed that applying low-intensity ultrasound at the resonant frequency induced deformation equivalent to that experimentally calculated in previous studies at higher intensities and a 1 MHz frequency. Additionally, the resonant frequency of an in vivo chondrocyte in healthy conditions, osteoarthritic conditions, embedded in a blood clot and embedded in fibrin ranges from 3.5 − 4.8 MHz. Conclusion: The main finding of this study is the theoretically proposed optimal frequency for clinical applications of therapeutic ultrasound induced cartilage restoration is 3.5 − 4.8 MHz (the resonant frequencies of in vivo chondrocytes). Application of ultrasound in this frequency range will maximize desired bioeffects